New insights on neurotransmitters signaling mechanisms in plants

ABSTRACT

Neurotransmitters (NTs) such as acetylcholine, biogenic amines (dopamine, noradrenaline, adrenaline, histamine), indoleamines [(melatonin (MEL) & serotonin (SER)] have been found not only in mammalians, but also in diverse living organisms-microorganisms to plants. These NTs have emerged as potential signaling molecules in the last decade of investigations in various plant systems. NTs have been found to play important roles in plant life including-organogenesis, flowering, ion permeability, photosynthesis, circadian rhythm, reproduction, fruit ripening, photomorphogenesis, adaptation to environmental changes. This review will provide an overview of recent advancements on the physiological and molecular mechanism of NTs in plants. Moreover, molecular crosstalk of SER and MEL with various biomolecules is also discussed. The study of these NTs may serve as new understanding of the mechanisms of signal transmission and cell sensing in plants subjected to various environmental stimulus.

Introduction

Neurotransmitters (NTs) such as acetylcholine, biogenic amines, indoleamines, and glutamine have been found not only in mammalians, but in all living organisms.^1,2 For the first time, acetylcholine,³ histamine,⁴ catecholamines, and SER^5,6 were discovered in plants. Apparently, the nature of signaling molecules has been conserved throughout living kingdoms. Mammals and plants share some similar chemical compounds and mediate cell function and translate these signals to survive and communicate. Earlier reports hypothesize a role of neurological signaling molecules in cellular communications in plants.⁷ NTs such as acetylcholine, ^8,9 catecholamines,¹⁰ γ-aminobutyric acid (GABA),^11,12 Indoleamines^13–26 have been reported in various plants.

Recently, a book has been published on NTs in plants and their prospective and applications.²⁷ This book highlights the role of NTs in plant development, stress adoption, interaction with other living organisms, and foods enriched with NTs. Recent reports suggest that NTs play an important physiological roles in plants such as delayed senescence, root and shoot induction, increased embryogenesis, promotion of fruit ripening, germ tissue protection, seed and pollen germination, and regulation of ion permeability.^28–30 NTs protect against stress and participate in intercellular and intracellular communications.³¹ The effects of MEL and SER on plant growth and development were depicted in Table 1. The biogenic amines exhibit a plethora of effects in the interface of plant, microbe and animal/insect interaction (biocoenosis), and stimulate microspore germination.¹ Dopamine exerts diverse allelopathic effects in terms of animal-plant or plant–plant interactions. The role of dopamine, histamine and acetylcholine in allelopathy and recognition provides potential insights to their ecological significance. The evolutionary perspective of this biomolecules in context to their biosynthesis genes and receptors are novel areas of investigations in plant neurobiology. The present review focuses on the recent developments of various NTs signaling mechanisms in plants. Moreover, it summarizes the role of NTs in plant growth and development, stress tolerance and ecophysiological behaviors.

Table 1.

Effects of melatonin and serotonin on plant growth and development.

Plant species	Effect	Reference
Melatonin Organogenesis and seed germination
Hypericum perforatum	Shoot multiplication and root induction	32
Chenopodium rubrum Arabidopsis thaliana	Suppression of flowering	33,34
Lupinus albus	Elongation of hypocotyls	35
Lupinus albus	Promotes adventitious and lateral root regeneration	36
Brassica oleracea	Improve seed germination	37
Lupinus albus	Stimulates the expansion of etiolated cotyledons↑ Tropic response	38,39
Mimosa pudica	Shoot multiplication and root induction	14
Brassica Juncea	Stimulate root growth	40
Cucumis sativus	Improve seed germination	41,42
Vitis vinifera	Seed growth and development	43
Prunus cerasus L.	Promotes adventitious root regeneration	44
Arabidopsis	Reduce root meristem size	45
Arabidopsis thaliana,Lupinus albus,Cucumis sativus	Increased number oflateral roots	46–48
Vigna radiata, Prunus sp., Lupinus albus, Oryza sativa, Arabidopsis thaliana, Helianthus annus Zea mays	Increased root elongation	44,46,49-51
Brassica juncea,Hypericum perforatum, Prunus rootstocks, Punica granatumCucumis sativus	Increased root number	32,40,44,52,53
Lupinus albus, Oryza sativa, Prunus rootstocks	Increased number of adventitious roots	44,46,49,54
Brassica juncea, Oryza sativa, Lupinus albus, Arabidopsis thaliana Triticum aestivum	Inhibition of primaryroot formation	40,49,50,55
Helianthus annus,Lupinus albus	Increased hypocotyl elongation	55,56
Phalaris canariensis,Avena sativaCapsicum annuum L.	Promotion of coleoptile Growth	35,58,60
Reproduction, Embryogenesis, and senescence
Coffea canephora	Induction of somatic embryogenesis	19
Malus sp., Arabidopsis thaliana, Hordeum vulgare, Oryza sativa	Delayed leaf senescence	61-65
Hypericum perforatum	Enhanced microsporeDevelopment	52
Prunus avium x Prunus cerasus, Oryza sativa, Arabidopsis thaliana	Increased plant biomass	44,49,50,66
Serotonin
Organogenesis, seed germination and regulation of senescence
Hypericum perforatum,	Increased shoot production	67
Mimosa pudica	Increased shoot formation	14
Coffea canephora	Increased incidence of somaticembryogenesis	19
Oryza sativa	Delayed senescence	68
Helianthus annuus	Increased root length	56,69
Hordeum vulgare	Increased root weight and root length, coleoptile weight and mitotic index	70
Arabidopsis thaliana	Increased lateral root formation and adventitious root formation, Inhibition of primary root formation	71
Helianthus annuus	Increased hypocotyl elongation	56
Hippeastrum hybridium	Promotion of germination	1
Juglans nigra x regia	Induction of root formation	72

Mechanism of action of neurotransmitters

Plants can also generate and transmit signals. Previous reports indicate that plants can produce electrical signals (impulses) that control important physiological processes, including photosynthesis, respiration, and movement of lateral organs. Plant-based NTs are structurally similar to those in animal cells and are identified in several plant species.⁷³ In case of animals, there are nerve tissues to transmit the signals. In plants the phloem cells particularly the companion cells that are present adjacent to the sieve tubes acts like the nerves as they have the continuous membranous structures. Calcium ion influxes, as well as potassium and chloride ion effluxes, are involved in the transmission of action potentials.⁷⁴ The main difference between the transmission of action potentials in animals and plants is that in an axon there is the potassium/sodium ion transmembrane transport, but in phloem cells, the potassium/calcium ion channels are involved in this process.⁷⁵

Acetylcholine signaling and crosstalk mechanisms in plants

Various investigations of acetylcholine crosstalk in relation with other phytoactive biomolecules have been recently reported in response to plant growth and development. The low levels of detection of acetylcholine in plant organs often pose a problem in its rapid analysis and quantifications. Biosynthesis of acetylcholine in plants has been depicted in Figure 1. Further investigations of the relation of acetylcholine with various phytohormonses shall elaborate its role as a potent morphogen. The fact that acetylcholine affects tropic response, cell division, and growth can be explained by deciphering its role as a positive/negative regulator (if any) for phytohormones especially auxin, gibberellins, and cytokinin. The effect of exogenous acetylcholine (Ach) (1 nM) on emergence and elongation of lateral root in Raphanus has been reported.⁷⁶ The effect of acetylcholine was observed to be possibly operative through a receptor mediated process which in turn altered the activity of primary metabolic enzymes. The malleability of the test was assessed by application of atropine (Acetylcholine receptor inhibitor) and neostigmine (acetylcholine esterase inhibitor). The effect of acetylcholine application was also manifested by increase in root biomass (dry weight). The effects of acetylcholine were investigated in etiolated seedlings in order to omit photomorphogenetic effects. The effect of exogenous acetylcholine in dark grown seedlings possibly operates through Pr form of phytochrome A [Phy A]. Therefore investigations on the crosstalk events associated with acetylcholine and phytochrome mediated response needs more attention in the present context. The effect of exogenous acetylcholine possibly increases nutrient translocation to stems and roots from the cotyledons. Application of atropine reversely affected root and stem elongation, thus suggesting its inhibitory role in Ach action in different organs. However, the effect of Ach on organ growth is not universally positive as being inversely reported.⁸ Exogenous Ach at concentrations of 10⁻⁴ M effectively reduced shoot growth and callogenesis in in vitro leaf explants of Lycopersicon esculentum. The effect was more pronounced in presence of neostigmine and acetylcholine being added together in the culture medium. Based on these morphogenetic effects of acetylcholine, authors consider it as a natural plant hormone. The signaling effects of ACh hydrolyzing enzyme acetylcholine esterase (AChE] have been investigated in response to rice shoot gravitropic response.⁷⁷ AChE has been stated to be a positive regulator of shoot gravitropism in rice seedlings. Gravity sensing in rice and maize seedlings is accompanied by asymmetric distribution of AChE activity in the regions of stele and cortex.^9,78-80 This has been attributed to be independent of auxin metabolism and does not act inhibitory to auxin. Arabidopsis seedling has been analyzed for acetylcholine profiling in various organs using liquid chromatography tandem mass spectrometric detection.⁸¹ The molecule was mostly detectable in the seeds and roots of Arabidopsis. It was furthermore observed that exogenous acetylcholine was found to be a negative regulator of root hair elongation in Arabidopsis. Subcellular level targets of acetylcholine have been identified in context of its role in modulation of expansin activity and cell elongation in tomato protoplasts.⁸² The combined effect of auxin and ACh was observed to elicit mRNA levels of expansin member LeEXPA2 (Tomato expansin genes) thus causing subsequent cell elongation. Interesting observations have been explained from investigations in Vicia faba which report the role of ACh in long distance signaling between root and shoot.⁸³ Osmotic stress downregulated acetylcholine biosynthesis in root tips. This molecule was also associated with signaling response in sensing of water potential levels and stomatal closure in response to osmotic stress. Mitigating effects toward osmotic stress has been observed with exogenous application of acetylcholine (0.5 mM) during seed germination in soybean.⁸⁴ The effects were measured in terms of root-shoot dry weight of seedlings subjected to a 1.0 MPa decrease in water potential. The current understanding of the ameliorating effects of exogenous acetylcholine in mitigating salt-stress has been substantiated by reports.⁸⁵ Exogenous application of acetylcholine (10 μM) in form of foliar spray and root absorption was effective in improving water status, gaseous exchange, photosynthetic ability, and antioxidative capacity of Nicotiana benthamiana plants subjected to 150 mM NaCl stress. Furthermore, acetylcholine-induced maintenance of chlorophyll synthesis was manifested by up-regulation of genes namely HEMA1, CHLH, CAO, and POR.⁸⁶ Amelioration of NaCl-stress was mostly effective through Ach-induced restriction in Na⁺ influx in seedlings. The fact that acetylcholine operates in multiple pathways of growth regulation and biomass accumulation is clear from recent investigations in various plant systems (Figure 2). However, further investigations are essential to understand the receptor mediated action of this biomolecule.

Figure 1.

Biosynthesis of acetylcholine in plants.

Figure 2.

Role of acetylcholine in plant signaling and communication.

Biogenic amines in plants

Biogenic amines are of three groups, i.e., catecholamines, tryptamines, and histamines. Biogenic amines such as histamine⁸⁷ and dopamine are also found in plants. Amines as biologically active compounds in ecosystems and having medicinal properties. Biogenic amines are involved in growth and development as well as in defensive reactions at stress.⁸⁸ Regulatory roles of biogenic amines were also reported in the reproductive behavior insects on plants such as rice.^89,90 The development of the insects depends on dopamine in plant bug Lygus hesperus.⁹¹ In tea leaves total biogenic amines profiles ranged from 2.23 μg g − 1 to 11.24 μg g − 1 and putrescine (1.05–2.25 μg g − 1) and spermidine (1.01 − 1.95 μg g − 1) were always present, while SER (nd–1.56 μg g − 1), histamine (nd–2.44 μg g − 1), and spermine (nd−1.64 μg g − 1) were detected more rarely.⁹² Black teas showed higher amounts of biogenic amines than green teas, and organic and decaffeinated samples contained much lower biogenic amines levels than their conventional counterparts⁹³, reported in Turkish brewed coffee total amine levels in the range 5.67 mg L − 1 to 48.88 mg L − 1. Putrescine, cadaverine, tyramine, and SER were detected in all coffee samples.

Catecholamine signaling in plants

In plants, catecholamines have been found in 28 species of 18 plant families.^1,88,94 The amount of dopamine found varies during plant development,⁹⁵ and sharply increases during stress.⁹⁶ The similar biosynthetic pathways of cathecholamines have been described both in plants and animals (Figure 3).⁹⁷ In plants, it is produced in the cytoplasm through the decarboxylation of glutamate.⁹⁸ Dopamine levels ranged from 80–560 mg/100 g in peel and 2.5–10 mg/100 g in pulp, even in ripened bananas.⁹⁹ Dopamine has been located histochemically in the latex vessels and in a few isolated parenchyma cells of banana ripened to the green-tip stage. Such fruit averaged 58.1 μg dopamine per gram of pulp compared to 24.5 μg per gram in halves of the same bananas at the fully ripe stage.¹⁰⁰ Increased amounts of dopamine (1–4 mg/g fresh mass) are found in flowers and fruits, in particular in Araceae species.¹⁰¹ This demonstrates the important role of the catecholamines as NTs in fertilization as well as in fruit and seed development. The presence of three catecholamines (norepinephrine, epinephrine, dopamine) and the biosynthetic precursors (DOPA and DOPS) were reported in the cotyledons of Pharbitis nil.¹⁰² GC-SIM analysis identified dopamine in P. nil seedlings (0.1–0.2 nmol/g fresh weight).¹⁰² L-Epinephrine, L-norepinephrine, and L-isoproterenol substantially promote flowering under a photoperiodic regime of 8-h light and 16-h darkness in Lemna paucicostata 6746.¹⁰³ The content of catecholamines differs significantly between different organs of potato and varies between leaves in different developmental stage.¹⁰⁴

Figure 3.

Catecholamine biosynthetic path way in plants. 1.Tyrosine decarboxylase; 2. Monophenol oxidase; 3. Tyrosine Hydroxylase; 4. Dopa decarboxylase; 5. Dopamine β-hydroxylase; 6. Phenyl ethonalamine N-Methyl transferase.

The role of catecholamines in plants is poorly known, but it is clear that they are involved in many aspects of growth and development. They were proposed as precursors for various alkaloids. Catecholamines are well known for their strong regulatory effect in animal systems, though little is known of their role in plants. In plants, adrenoreceptors participate in cytoplasm movement, ion permeability, and membrane potential, in flowering of Lemna paucicostata, photophosphorylation, as well as the seed and pollen germination.⁸⁸, ^94,105 Effects of catecholamines and their derivatives on gibberellic acid (GA)-induced lettuce hypocotyl elongation were reported.¹⁰⁶ The catecholamine compounds in potato (Solanum tuberosum L.) leaves and tubers have been identified by gas chromatography coupled to mass spectrometry (GC-MS) measurements.¹⁰⁴ Under stress conditions, the normetanephrine level and catecholamine catabolism were significantly decreased. Increased catecholamine level in potato resulted in enhanced pathogen resistance. Plant catecholamines are involved in plant responses toward biotic and abiotic stresses. Dopamine biosynthesis at different stages of plant development was reported in Papaver somniferum. Dopamine biosynthesis in latex and cell-free extracts also varied with the stage of organ development. L-Epinephrine, L-norepinephrine, and L-isoproterenol substantially promote flowering under a photoperiodic regime of 8-h light and 16-h darkness in Lemna paucicostata 6746.¹⁰⁸

A defense function for catecholamines in the plant cell has also been reported.^1,88,94,104 In order to observe similar response occurs in plants, leaves of potato plants were wounded and catecholamines levels prior to and 5, 10, and 13 min after wounding were determined. There was a consistent increasing trend in concentration of dopamine, norepinephrine, and normetanephrine.⁸⁸ Similarly, increase in norepinephrine was measured in potato leaves subjected to ABA and water stress treatment.

Metabolic regulations of dopamine in plants: Redox signaling and oxidative stress modulation

Recent advancements suggest the role of dopamine in physiological regulations associated with hormonal metabolism, ion homeostasis, and detoxification of oxidative radicles. These primary events essentially regulate tolerance toward biotic or abiotic stress in plants. Dopamine-induced elevation in superoxide dismutase activity and subsequent reduction in ROS levels and lipid peroxidation has been reported in soybean roots.¹⁰⁹ The antioxidative role of this biomolecule has been reported.¹¹⁰ The allelopathic effect of dopamine has also been observed to be growth inhibitory for soybean roots.¹¹¹ The potential role of dopamine against herbivory defense, nitrogen fixation, IAA oxidation, and flowering has been reported earlier.^{103,107,112,113} Interestingly, the role of dopamine in ion permeability and photosynthetic efficiency¹¹² provide insights of its physiological implications in signaling process. Dopamine-induced IAA oxidation also remains as one of the crucial modulatory effects that might relate to alteration in the action of the phytohormone.^107,114 Dopamine-induced root inhibition has been attributed to higher auxin levels in the roots caused by inhibition of IAA oxidase activity.¹¹¹ Authors also state the possibilities of ROS and melanin production as reasons for dopamine-induced root growth modulation. The effects of exogenous dopamine can, therefore, exert dual effects of both ROS reduction as well alteration in the hormone metabolism and ROS surge. Dopamine regulates phenylpropanoid pathway and activities of phenylalanine ammonia lyase (PAL) or tyrosine ammonia-lyase (TAL) in roots.¹¹⁵ Microarray analysis, revealed the role of dopamine in alteration of expression of more than 170 genes associated with biotic and abiotic stress.¹¹⁶ Interestingly, some of the upregulated genes encoding ion transporters were associated with ion homeostasis of Zn, Cu, and Fe. Other candidate genes were associated with amino acid metabolism and lignin synthesis,¹¹⁷ discussed the contradictory/dual role of dopamine acting both as a prooxidant and antioxidant,¹¹⁸ inferred the role of L-dopamine in inducing salinity tolerance in rice. The tolerance mechanism was operative through better water retention and decreased sodium uptake. The effect of exogenous dopamine was manifested by downregulation of OsPIP-1 and subsequent water permeation ability. Multiple metabolic regulations exerted by exogenous dopamine toward nutrient and salinity stress alleviation have been reported in Malus huphehensis.¹¹⁹ Similar effects of exogenous dopamine have been reported to regulate nutrient uptake, ion transport, and inhibition of senescence in Malus huphehensis subjected to drought stress.¹²² Application of exogenous dopamine (100 µm) led to improved mineral uptake and higher photosynthetic ability in plants subjected to nutrient deficiency. Dopamine-induced alleviation of oxidative stress was manifested in the form of increase in antioxidant enzyme (Ascorbate-glutathione cycle) gene expressions. Alternatively, the senescence genes were downregulated by dopamine. The prooxidative nature of dopamine leads to free radicle formation (semiquinone), melanin synthesis, and ROS burst which, however, appears to be growth inhibitory. Dopamine-induced increase in lignin synthesis associates with lower levels of hydrogen peroxide in roots.¹²³ Thus root growth regulation affected by L-dopamine results from multiple mechanisms. Extensive investigations by,¹²⁴ reported differential gene expression in response to exogenous dopamine application in water-stressed Malus domestica Borkh. Dopamine-induced regulation of gene expression mainly altered genes associated with nitrogen, secondary compounds, and amino acid metabolism. Regulation of transcription factors, namely, WRKY, ethylene response factor ERF, and NAC were also associated with dopamine-mediated regulation of drought tolerance. Calcium-signaling mediated drought tolerance was evident through increased expression of cyclic nucleotide gated channels (CNGC) and CAM/calmodulin-like (CML) family genes. Further investigations are necessary for deciphering receptor mediated signaling response of dopamine. Aforementioned evidences, therefore, suggest that phyto-dopamine remains associated in crosstalk with phytohormones and other associated biomolecules involved in regulation of plant metabolism (Figure 4).

Figure 4.

Physiological role of dopamine in plants.

Molecular mechanisms of GABA action in plants

The various plant signaling responses exhibited by GABA mostly associate with carbon and nitrogen metabolism, TCA cycle, nutrient starvation, and pathogen interaction and abiotic stress^125-128 (Figure 5). Modulation of Ca2+ levels in plants has been reported to be a downstream action of GABA-induced response. The positional significance of GABA in plants appears to be in the interface of carbon and nitrogen metabolism.¹²⁶ The GABA shunt explains GABA biosynthesis in plants bypassing two steps of TCA cycle. GABA synthesis is also triggered by polyamine degradation or non-enzymatic reaction from proline during oxidative stress.^130–132 GABA catabolism in mitochondria elicites another cascade of downstream signaling by producing Succinic-semi aldehyde (SSA) catalyzed by the action of GABA transaminase enzyme.^130,131 The GABA shunt has been reported to possess a significant role in GABA signaling and link between N and C metabolism.^127,133 This has also been attributed to be a major source of succinate in mitochondria of leaf cells during the day time.¹²⁷ The GABA receptor genes functional in plants encode structural domains homologous to animal GABA receptors.¹³⁴ Quantum dot-mediated GABA-binding sites have been evidenced on the surface of pollen and somatic protoplasts thus suggesting receptor mediated signaling response mediated by GABA. This was further substantiated by the evidence of transient surge in [Ca²⁺]_cyt triggered upon binding of QD-GABA probes.¹³⁵ Ca²⁺-CaM involvement in GABA signaling has also been reported to be essential for agrobacterium–plant interaction.¹³⁶ GABA activity induced by biotic stress operates through modulation of arginine decarboxylase activity which in turn triggers hydrogen peroxide, nitric oxide, and polyamine synthesis.^125,128 GABA accumulation in starved plants may be associated with subsequent succinate formation in mitochondria which serves as a source of electron in respiratory pathway,¹³⁷ suggest that GABA receptors are involved in nutrient uptake and growth promotion in plants. The metabolism of GABA is partitioned between mitochondria and cytoplasm.¹²⁶ A significant contribution on the mechanism of GABA action has also been reported.^138,139 The downstream action of GABA has been reported to be operative through modulation of aluminum activated malate transporters (ALMT) in plants. This in turn affects root growth and pH tolerance in wheat roots in response to aluminum stress.¹³⁹ GABA regulated malate efflux rates from wheat roots are subjected to Al²⁺ stress and low pH. GABA was observed to be a negative regulator of Al²⁺ activated malate transporter protein which, however, is also pH-dependent in nature. Changes in the membrane potential triggered by GABA-mediated ALMT activity is a primary event responsible for transducing downstream response in cells. The GABA-mediated modulation of ALMT family proteins is a conserved feature analyzed in various plant systems like Arabidopsis, rice, soybean, etc. However, all of them may not be specifically associated with Al²⁺ activation and malate efflux. Malate ion retention in root cells induced by abiotic stress-mediated GABA action proves beneficial toward stress amelioration. However, malate retention in alkaline soil appears to be more beneficial for the plant roots. The fact that GABA regulates anion channels at physiological concentrations is beneficial for crop improvements and their stress acclimatization.¹³⁹ In silico evolutionary coupling, analysis revealed that ALMT proteins bear GABA-binding sites at the N-terminal domain. The effects of GABA-mediated ion channel modulation and membrane hyperpolarization occur in a way similar to that of animal cells.

Figure 5.

Physiological role of GABA in plants.

A comparison of plant-based GABA receptors and mammalian GABA_A receptors in terms of molecular identity, mode of action, and signaling response have been reported.¹³⁸ Recent reports in the last couple of years have substantiated the potential role of GABA in eliciting stress tolerance through its involvement in multiple signaling pathway. Mitochondrial malate metabolism, post-harvest storage, osmotic regulation and regulation of ion homeostasis are likely to be associated with GABA signaling in plants. GABA-mediated phenolics accumulation in hulless barley seeds is essentially mediated by the activity of Ca⁺ signaling pathways.¹⁴¹ Recent investigations on the action of GABA in plant signaling pathways decipher its persuasive role as an important target for plant proteins,¹⁴² have attempted to optimize methodologies to detect GABA-binding proteins in plants. Immobilization of the free carboxylic group of GABA into magnetic beads (SiMAG-Carboxyl) might be fruitful in preparing suitable probes for imaging GABA receptors in plants. According to,¹⁴³ exogenous GABA essentially imparts tolerance to salinity-alkalinity stress by regulation of redox homeostasis and chlorophyll biosynthesis in muskmelon. GABA possibly reduced the levels of stress-induced H₂O₂. NaCl-stress induced osmotic imbalance is alleviated by GABA-induced expression of dehydrin genes (SK2, Y2 K, Y2SK, and dehydrin b) in white clover seedlings.¹⁴⁴ Exogenous GABA at a concentration of 5 mM has been reported to impart cold tolerance to tea plants.¹⁴⁵ iTRAQ-based proteomic analysis revealed GABA-induced regulation of genes associated with nitrogen metabolism, carbohydrate metabolism, and subsequent alteration in certain metabolites like glutamate, polyamines, and anthocyanin. GABA possesses potential effects as a thermo-protectant in heat-stressed mung beans.¹⁴⁶ GABA-treated plants exhibited better retention of photosynthetic activity and higher osmolyte accumulation during heat stress. UV stress-induced GABA accumulation has been deciphered to be triggered by NO and cGMP-mediated pathways.¹⁴⁷ Although the nature of receptor mediated primary signal response of GABA is similar in plants and animals there are different downstream proteins involved in both the systems. Novel insights, therefore, suggest the evolutionary significance of GABA receptors and GABA-binding ion channels operative in plant, animal, and fungal groups. Future perspectives include more detailed investigations and cross-talk mechanisms of GABA-mediated response in plants. This shall further enhance the understanding of its mode of action in plant growth, nutrient balance, stress tolerance, and reproduction.

Melatonin as a biomarker of plant stress signaling

MEL a major indoleamine in plants exhibits a plethora of effects in biotic and abiotic stress acclimatization.^57,27 The mechanism of action of MEL has been reported to be operative at gene, protein, or hormonal levels. MEL has potent antioxidative property by the virtue of its free radical quenching ability. The 5-methoxy and 3-amide group associated with the indole ring of MEL provides it the structural uniqueness for free radical (ROS, RNS, OH⁻, and H₂O₂) quenching.¹⁴⁸ MEL potentially upregulates the gene expression of antioxidant enzymes thus triggering efficient detoxification mechanisms.^149,150 Among various effects of MEL in plants, biotic and abiotic stress acclimatization has been reported to be operative through various mechanisms (Table 2). Arabidopsis has been investigated for the exogenous effects of MEL altering the expression of defense-related genes.¹⁸² Interestingly the genes upregulated or downregulated by MEL exhibited differential sensitivity with respect to its concentration. This signifies differential regulation of MEL operative toward defense response at its low and high concentrations in Arabidopsis. Upregulated genes were associated with stress receptor kinases, calcium signals and hormones, namely, ABA, ethylene, and salicyloic acid. These exhibit different mechanisms of MEL-mediated tolerance toward abiotic and biotic stress. Overexpression of C-repeat binding factors in response to exogenous MEL has been reported to confer biotic stress tolerance in Arabidopsis.¹⁸³ Interestingly in Arabidopsis MEL-mediated surge in nitric oxide is responsible for triggering innate immunity against Pseudomonas syringae pv. tomato.¹⁸⁴ Moreover, INDOLE-3-ACETIC ACID INDUCIBLE 17 (IAA17) is a positive modulator of natural leaf senescence and provides direct link between MEL and AtIAA17 in the process of natural leaf senescence in Arabidopsis.¹⁸⁵ The malleability of MEL-mediated NO response was tested using NO scavenger and NO-deficient mutants susceptible to the bacterial infection. MEL biosynthesis from SER catalyzed by the activity of n-acetyl SER transferase triggers upregulation of salicylic acid biosynthesis. These events are important in conferring resistance against Pseudomonas syringae pv. tomato.¹⁸⁶ SNAT mutants exhibited lower amount of SA accumulation thus causing increased susceptibility to the avirulent pathogen. Exogenous MEL application (10 µm) in tobacco and Arabidopsis induced expression of pathogenesis related (PR) genes associated with SA and ET synthesis.¹⁸⁷ Thus, MEL-mediated biotic stress defense exhibits dependency on salicylic acid and ethylene action downstream to MEL induced gene expressions. In similar investigations by¹⁸⁸, MEL (1 µm) induced mitogen activated protein kinase (MAPK) response was associated to innate immunity response independent of G-protein signaling. Interestingly, MEL triggers expression of heat shock proteins 90 s in banana (Musa acuminate) which confers tolerance toward Fusarium wilt (Fusarium oxysporum) by acting through auxin signaling.¹⁸⁹ Therefore, evidences suggest MEL-auxin crosstalk in biotic stress modulation mediated by the expression of heat shock proteins. MEL induces downstream SA action effective toward biotic stress tolerance to species of fungal pathogens, namely, Alternaria, Botrytis, Phytopthora, or Penicilllium.⁵⁷ Upregulation of endogenous MEL biosynthesis is triggered by RAV transcription factors associated with bacterial blight tolerance in cassava.¹⁹⁰

Table 2.

Exogenous melatonin improves abiotic stress tolerance in different plants.

Plant speices	Function	Reference
Chenopodium rubrum	Photoperiodic eventsCircadian rhythms	151
Hypericum perforatum	Regulation of the reproductive physiology andflower development	52
Daucus carota	Anti-apoptotic effect	152
Glycyrrhiza uralensis	Tolerance to photodamage and UV-B	129
Eichhornia crassipes	PhytoremediationTolerance to photodamage and UV-B	153
Brassica juncea	Protecting reproductive tissues from oxidative damage caused by abiotic stress	154,155
Brassica oleracea	Protect seedlings against toxic copper ions	37
Hordeum vulgare	Protective effect of against chlorophyll degradation during senescence and chemical stress	61
Cucumis sativus	Improves germination during chilling stress	15
Datura metel	Protective role in developing flower buds	156
Vigna radiata	Defend effects ofMEL on UV-B irradiation	157
Cucumis sativus	Protective effect under high temperature stress	191
Rhodiola crenulata	improves the survival of cryopreserved callus	158
Malus domestica	Delayed senescence	63
Solanum lycopersicum L.	Salinity	159
	Drought tolerance	172,192
	Thermo tolerance	160
Zea mays	Salt stress tolerance, protects photosystem II from drought stress	51,161
Prunus persica	Drought stress tolerance	162
Malus hupehensis rehd.	Alleviates alkaline stress	163
Prunus persica	Reduces chilling injury	164,59
Actinidia deliciosa seedlings	Heat tolerance	165
Camellia sinensis L	Alleviates cold stress	166
Avena sativa	Drought stress, salt stress	167
Medicago sativa	Drought stress	168
Helianthus annuus L.	Salt stress	169
Cucumis sativus[in saline conditions)	↑ GA biosynthesis genes↑ Germination rate	149,53
Hordeum vulgare leaves [in drought/cold]	↑ Photosynthesis efficiency ↑ Resistance to drought, cold	170
Perennial ryegrass leaves (Lolium perenne] (in heat-induced senescence)	↑ Photosynthesis efficiency↑ Cell membrane stability↓ Senescence	193
Solanum lycopersicum L. plants	↑ Ascorbic acid, lycopene, Ca, P ↑ Quality and yield of tomato fruits, defense to salt stress	171,173
Solanum lycopersicum L. fruits	↑ Ethylene,, flavors, lycopene, ↑ ACC synthase genes, anthocyanins↑ Ethylene receptor genes	174,175
Fragaria sp. fruits	↓ Post-harvest senescence ↑ ATP, antioxidants, shelf-life	140
Prunus persica fruits	↓ Post-harvest senescence↑ Weight, firmness, ascorbic acid	164
Brassica rapa	Delays senescence, ↓ chlorophyll catabolism and ↓ ABA biosynthesis genes	176
Triticum aestivum	NO-mediated tolerance to cadmium stress	60
Capsicum annuum L.	Defense to salt stress	177
Catharanthus roseus	Combats cadmium stress	178
Nicotiana tabacum L.	Cadium tolerance	179
Brassica napus	Transcriptomic regulation of salt stress	180
Coffea arabica L.	Reduces oxidative damage and confers tolerance to drought stress	181
Limonium bicolor	Improves seed germination under salt stress	194

Abiotic stress tolerance in response to MEL has undergone recent developments in various model systems investigated in response to salinity, drought, and thermo-tolerance.¹²⁰ The mechanisms of melatonin mediated action involve multiple regulations through hormone response, transcriptional control, ion homeostasis, and oxidative detoxification. MEL upregulates Core binding factor (CBF) and Dehydration responsive element binding (DREB) elements thus conferring cold stress tolerance in Arabidopsis.^50,183 Water stress alleviation in Cucumis sativus has been reported to be mainly mediated by higher seed germination rate, increased root-shoot ratio, and elevation of ROS scavenging antioxidant enzymes.⁴⁷ Rice mutants for MEL biosynthesis pathways (SNAT and ASMT) were observed to show growth reduction in seedlings and increased susceptibility to salt and cold stress.¹⁹⁵ The authors also stated that MEL regulates coleoptile growth in anaerobic or anoxic conditions. Proteomic analysis of MEL induced changes in Bermuda grass has revealed the upregulation of carbohydrate metabolism, photosynthesis rate, and amino acid biosynthesis in response to oxidative stress.¹⁹⁶ Detoxification of cellular H₂O₂ induced by MEL is also accompanied by decrease in chlorophyll degradation and suppression of senescence in rice plants, ^197,198 reported that MEL restored structural integrity of chloroplasts following H₂O₂ detoxification during water deficiency in grape cuttings. Acetylserotonin O-Methyltransferase (ASMT) overexpression transgenic in Arabidopsis conferred drought tolerance in Malus by overproduction of MEL in a single diurnal cycle of 24 h66. Metabolically engineered Arabidopsis with ectopic expression of SNAT gene in mitochondria revealed the organelle to be an important site of MEL biosynthesis similar to animals.¹⁹⁹ The expression of SNAT was also induced by drought stress. Tolerance to salinity and heavy metal stress mediated by MEL is mostly operative through redox balance, ion homeostasis, and improvement of photosystem functionality.^173,200-202 MEL-cytokinin crosstalk has been reported in the context of drought stress alleviation and suppression of leaf senescence in Agrostis stolonifera.²⁰³ The application of exogenous MEL has been known to upregulate cytokinin signaling genes and subsequently, it down-regulates chlorophyll degrading genes. ¹⁸³, reported that primary metabolic homeostasis induced by MEL in Bermuda grass is operative for nitrogen and carbohydrate metabolism, tricarboxylic acid cycle transformation and photorespiration. MEL induced regulation of seedling growth in soybean induced by abiotic stress primarily operates through primary metabolism and antioxidative machinery.²⁰⁴ Moreover, Salt stress-induced seedling growth inhibition and coincides with differential distribution of SER and MEL in sunflower seedling roots and cotyledons.⁵⁶ Recent developments, therefore, reveal diverse physiological and metabolic responses triggered by MEL in response to biotic and abiotic stress. Recent advancements in the aspects of MEL-mediated crosstalk associated with various plant growth regulators have been reviewed by.²⁰⁵ MEL in the context of NO signaling has been reported to be associated with the formation of nitroso-melatonin which is associated with stress tolerance, long-distance signaling, and fruit ripening responses.²⁰⁶ MEL induced abiotic stress tolerance mostly operates through the modulation of various hormonal pathways associated with auxin, ABA, brassinosteroids, GA, and cytokinin.^182,207,193 A possibility of receptor mediated MEL signaling has been reported by²⁰⁸. Interestingly the downstream action of MEL-CAND2 receptor binding was transduced in form of H₂O₂ formation and generation of calcium flux.

According to,¹⁷⁶ exogenous MEL treatment has been observed to elicit changes in the transcriptome of hormonal pathway of salt-stressed rape seeds. Further changes associated with MEL treatment were associated with the lipid and fatty acid signaling pathways. Thus the findings summarize the potential role of MEL in imposing intrinsic regulation of hormone network and subsequent stress tolerance.²⁰⁹, identified Dehydration responsive element binding (DREB1α) and IAA3 as the potential downstream transcription factors which can impose MEL-mediated alkaline stress tolerance in tomato plants. The expression of MAPK3, MAPK4, MAPK6, and salt overly sensitive (SOS) genes (SOS1, SOS2, SOS3) have been reported to be increased in response to exogenous MEL in salt-stressed cucumber plants.⁵³ An important discussion appears in the review by ²⁹, where the authors are suggestive of the fact that MEL can possibly be considered as a new phytohormone.

Molecular crosstalk of serotonin and melatonin with various biomolecules

Various critical reviews have summarized the role of SER and MEL in regulating the activity of other biomolecules in plants.²¹⁰ The complex network of signaling response has been mostly confirmed by pharmacological, genomic, transcriptomic, and metabolomic analysis of various plant systems.^182,205 SER has been reported to possess various derivatives in plants¹⁵⁶ which, however, exhibit less dynamic effects in comparison to the physiological response exerted by MEL. Long-distance signaling role of SER and MEL being associated with JA, SA, and NO has been reported in various plant systems.¹⁸³ However, much remains to be deciphered about the complex nature of communication of these indoleamines with various phytohormones and other metabolites. Possibilities lie in the fact that auxin receptors may be surrogated by MEL which is known to trigger similar kind of responses in plant growth and morphogenesis. SER has been reported to exhibit both growth promoting and inhibitory effects in plants.⁷¹ Furthermore, it is involved in the complex regulation of root tip architecture.^211–215 Recent review by the author has elucidated the signaling role of SER and ROS in association with JA and ABA crosstalk.²⁰⁵ Auxin and MEL biosynthesis are regulated by the complex regulation of tryptophan metabolism and the activity of tryptophan decarboxylase which appears to be a rate-limiting enzyme. The activity of TDC is under the precise regulation of photomodulation, temperature, and osmotic stress in plants.²⁰⁵ MEL has been reported to alter the expression of IAA/IBA genes and auxin efflux proteins such as PIN1, PIN3, PIN7, IAA19, and IAA24.²¹⁶ Mediator proteins have been known to be associated with the crosstalk between cytokinin and MEL activity.²¹⁷ Recent findings have deciphered the unique signaling interaction between MEL and brassinosteroid in rice seedlings.²⁰⁷ The review by ²⁰⁵, has discussed the critical involvement of MEL in stress amelioration, MAPK signaling, ROS homeostasis in association with JA, NO and SA. A brief understanding of the crosstalk mechanism between nitric oxide and MEL has attained some advancement in a recent couple of years. NO-MEL interaction in tomato is mediated by hydrogen sulfide signaling which imparts tolerance to Fe deficiency and NaCl stress.⁶⁰ The synergistic and antagonistic effects of MEL and hydrogen sulfide have been reported to modulate MEL-ABA crosstalk.²¹⁸ Various instances of NO-MEL crosstalk have been discussed in the review by ²⁹, which involve MAPK and hydrogen peroxide signaling. Future investigations are expected on the aspect of N-nitrosomelatonin formation and its possible function in plants.²¹⁹ The Crosstalk events associated with SER and MEL were shown in Tables 3 and 4.

Table 3.

Crosstalk events associated with serotonin in plant signaling.

Signaling response	Response	Reference
PIN efflux family proteins	Differential expression, SER elicits auxin like action	71,220
Jasmonic acid	Induces JA synthesis, JA mutants [COI 1 and JAR 1) exhibit reduced SER sensitivity	215
Reactive oxygen species	SER induced ROS surge and its differential redistribution in roots	215
Ethylene	Positive regulator for root development. Etr 1 mutant with poor sensitivity to SER	215
Free radical species [ROS, RNS, singlet oxygen]	Induces localized hypersensitive response toward biotic stress	221
Methyl jasmonate [exogenous]	Induces SER biosynthesis genes to overexpress	222
ABA [exogenous]	Induces SER biosynthesis genes to overexpress	222
Biotic stress [aphid infestation]	Induction of Trp decarboxylase gene in response to aphid infestation in leaves	223
Thermal stress	Redistribution of SER in cells accompanied by polar redistribution in root tips	30
Biotic stress	SER mediates insect infestation-mediated defense signaling	179
Plant defense	Activity of SER N-acetyltransferase [SNAT] is essential for downstream MEL accumulation and fungal defense	224
Triggering of flowering and MEL accumulation	Knockout analysis of Arabidopsis SER N-acetyltransferase [SNAT] reveals its role in flowering and MEL accumulation	225
Seed development and organogenesis	RNAi silencing of SER N-acetyltransferase [SNAT] isogenes reduce MEL accumulation and reduce seed development in rice.	226

Table 4.

Crosstalk events associated with melatonin in plant signaling.

Signaling event	Response	Reference
Auxin response elements	Down regulation of Auxin Resistant 3 (AXR3]/Indole-3-Acetic Acid inducible 17 [IAA17) response	185
Auxin conjugation pathway	Up regulation of GH3 genes [IAA-aminosynthase enzyme] catalyzing aminoacid conjugation to auxin.	182
Auxin efflux transporters	Alteration in the expression of IAA/IBA genes and efflux transporters namely PIN1, PIN3, PIN7, IAA19, and IAA24	216
Auxin induced transcription	Auxin associated transcription factors, namely WRKY, NAC, myeloblastosis (MYB) are altered in activity	227
Auxin biosynthesis	YUC1, YUC2, YUC5, YUC6, and Tryptophan Aminotransferase (TAR2) get down regulated	45
Cytokinin induced senescence	Down regulation of senescence genes namely LpSAG12 and Lph36	193
Cytokinin biosynthesis	Up regulation of cytokinin biosynthesis genes [LpIPT2 and LpOG1]	193
Cytokinin responsive transcription factors	Changes in expression patterns of A-ARRs and B-ARRs	193
Cytokinin – PR protein interaction	PR-10 investigated to be a low affinity MEL binder	217
Gibberellic acid pathway	Up regulation of gibberellins pathway [GA] genes like D-limonene synthase, Gibberellin 2-oxidase	228,194
GA biosynthesis genes	Up regulation of GA20ox and GA3ox	47,149
ABA biosynthesis	Down regulation of enzyme 9-cis-epoxycarotenoid dioxygenase [NCED], LpZEP and LpNCED1	193
ABA receptor	Down regulation of Abscisic acid receptor PYL8	228
Salicylic acid biosynthesis	Up regulation of isochorismate synthase-1 [ICS-1]; SA biosynthetic enzyme	188
Kinases	Immune response triggered by mitogen-activated protein kinase (MAPK] and OXI1 [oxidative signal-inducible1) kinase pathway	188
Nitric oxide	Differential modulation of Cu/Zn and Mn SOD isoforms	169
	Glutathione homeostasis	229
Ethylene biosynthesis	Up regulation of aminocyclopropane- 1-carboxylic acid [ACC] synthase expression	175
Ethylene receptor	Up regulation of ethylene receptor genes, NR and ETR4, and signaling mediator elements, EIL1, ethylene-insensitive3-like (EIL3) and ERF2.	175
Brassinosteroids	Up regulation of DWARF4, a rate limiting BR biosynthetic gene	207
Polyamines [putrescine, spermidine]	Triggering NO biosynthesis	230,231
Hydrogen sulfide and NO	Induces tolerance to Fe deficiency and NaCl stress	60
Hydrogen sulfide, ethylene and NO	Regulates fruit ripening	206
Ethylene	Inhibition of the activity of aminocyclopropane-1-carboxylic acid synthase]	232

Histamine in plants

Histamine was first found in the ergot fungus Claviceps purpurea, and subsequently in many bacterial and plant cells.^4,233 The amount of histamine varies according to the phase of plant development. For example, in the marine red algae Furcellaria lumbricalis (Huds.) the occurrence of histamine was from 60 to 500 mg/g fresh mass.⁸⁷ The amount of histamine (in mg/g fresh mass) in the male plant was 90–490 (sometimes up to 1,100), in the female plant 60–120, and in asexual tetra sporophyte 100–500. For all living organisms, the biosynthesis pathway of histamine includes histidine decarboxylase which participates in the decarboxylation of histidine.^1,234,235 The gene encoding histidine decarboxylase (hdcA) has been identified in different Gram-positive bacteria.²³⁵ Catabolism of histamine occurs also via methylation or acetylation in the presence of histamine-N-methyltransferase, or histamine- N-acetyltransferase, and genes cording of the enzymes have been found in bacteria, plants, and animals.²³⁶ Histamine derivatives viz. N-acetylhistamine, N, N-dimethylhistamine, and feruloylhistamine are also found in plants. Especially high levels are observed in species of the family Urticaceae. The Brazilian stinging shrub Jatropha urens (family Euphorbiaceae) contains 1,250 mg histamine per 1,000 hairs. The presence of histamine in stinging hairs is a protective mechanism that serves order to frighten off predatory animals by inducing burns, pain, and allergic reactions. Under stress conditions, a sharp increase of histamine is observed in plants, as in animals.²³⁷, have determined the histamine content of some commercial vegetable pickles at the range of 16.54 and 74.91 mg/kg (average 30.73 mg/kg). The maximum value (74.91 mg/kg) was obtained from a sample of hot pepper pickles.

Glutamate signaling in plants

The important signaling role of Glutamate (Glu) in animal systems has been known for more than 50 years, but little is known about the role of glutamate in plants.^238,239 Recent reports suggest that Glutamate plays important roles in plant nutrition, metabolism, and signal transduction. In addition to genes involved in metabolism, transport, growth, and signal transduction, glutamate rapidly induces the expression of genes related defense and stress responses.^240,241 Glutamate may have a role similar to an elicitor or the exogenous glutamate may affect the cell wall and triggers an elicitor-like response in the plant cell. In Arabidopsis, in response to aluminum, Glu binds a ligand-gated calcium channel and triggers calcium influx that induce depolimerization of microtubules and depolarization of the plasma membrane to inhibit root elongation.²⁴² Besides, Glu treatments alter root architecture inhibiting primary root through reducing meristem mitotic activity and induce lateral root proliferation.^243,244 Moreover, Glu and its crosstalk with other factors affecting the root development, such as phosphorous, auxin, ABA (Abscisic Acid), and nitrate. Ion channels of the GLUTAMATE RECEPTOR–LIKE family act as sensors that convert this signal into an increase in intracellular calcium ion concentration.²⁴⁵ In maize seedlings, Glu pretreatment enhanced the survival percentage of maize seedlings under heat tolerance.²⁴⁶ Recently, the effect of Glu in plant growth, development, and response and adaptation to environmental stress was reviewed by ²⁴⁷. Glu was found to induce seed germination ²⁴⁸, root architecture, ²³⁹ pollen germination, and pollen tube growth²⁴⁹ and adaptation to abiotic stress^{144,228,245,246,252}, reported that, when Arabidopsis was wound by herbivores, Glu, released from phloem cells. Exogenous l-glutamate treatment could induce resistance against Penicillium expansum in pear fruit.²⁵³

Role of neurotransmitters in biocoenosis and allelopathy

The evolutionary considerations of NTs in various signaling response have been widely discussed across microbes, plants, and animal systems. Among various important non-neuronal role of NTs chemo-signaling and recognition bear holistic ecological significance. Structural complexity of living organisms, ecological interactions, and associations with community assemblages are some of the factors which determine the role of NTs. In the context of plant–plant relation (phytocoenosis), NTs have been reported to regulate pollen allelopathy and pollen recognition processes.^1,105,254 The temperate green algae Ulvaria obscura exhibits antiherbivore defense induced by dopamine production.¹¹³ This bloom forming alga secretes dopamine in sea water which regulates germination of other brown algae and invertebrate larvae in a concentration-dependent manner. Fluorescent model systems have been developed using microspores of Equisetum arvense and Hippeastrum hybridum for in-vivo analysis of allelopathic NTs.²⁵⁵ The authors report preliminary experiments to study their possible role in biocoenosis. The secretions influence plant-microbe-animal interactions. Dopamine, norepinephrine, and SER at high concentrations (10^-5 M) stimulated pollen germination in Equisetum arvense and Hippeastrum hybridum.²⁵⁶ Implying fluorescent methods these unicellular haploid model systems can therefore be used to study the role of these amines in allelopathic interaction. High concentrations of endogenous dopamine have been reported in Mucana pruriens and Vicia faba. Wild populations of M. pruriens are been used for industrial extraction of dopamine. This non-protein amino acid protects the bean plants from attack of mammals and insects. Root exudations containing dopamine can raise upto 50 ppm in vicinity of other roots. Southern armyworm larvae being fed with velvet bean (Mucana pruriens) seeds or synthetic dopamine exhibited increased mortality.^257,258, explains the precise role of soil type and pH regulating the stability, adsorption, and chemical transformation of allelochemicals, namely, catecholamines. Investigations in volcanic ash soil revealed higher transformation of dopamine in presence of high pH and soil adsorption ability. Specific strains of Pseudomonas syringae respond to extracellular plant-based acetylcholine in addition to choline as a source of osmoticum. The molecule undergoes its turnover in the periplasmic space and cytoplasm of bacterial cells. This evidence puts forward new developments in the potent role of acetylcholine in plant–microbe interaction.²⁵⁹ Importers of choline uptake used by specific microbial strains attribute to their wide habitat distribution and success of colonization. Application of exogenous acetylcholine and histamine promote pollen germination in Hippeastrum hybridum thus suggesting physiological competency of pollen-pistil recognition induced by this allelochemicals.²⁶⁰ Cyperus rotundus (one of the notorious invasive weed) has been reported to exude strong inhibitors toward acetylcholine esterase activity which affects herbivory and growth of other plants in its vicinity.²⁶¹

Nutraceutical importance of neurotransmitters in plants

The dietary role of plant-based NTs has been investigated since last few decades. The potential role of SER, MEL, dopamine, histamine, or acetylcholine has been elaborated in various investigations.²⁶² These biomolecules have been reported to alter brain functioning, mood regulation, and normalization of cardiovascular functioning. Various plants have been reported to contain high amount of biogenic amines like SER, MEL, and norepinephrine.^263,264 The authors state that bananas and walnuts are the major source of dopamine and SER among various plant products. The fact that various source of animal and plant-based products vary in their MEL content has been attributed to climatic and environmental factors. MEL content has been reported to vary from picograms to microgram levels across wide variety of plant products including cereals, fleshy fruits, and seeds.^22,265-269 The dietary value of MEL in food largely depends upon the culinary methods implied for consumption. These are mostly boiled cooking, fried, fermentation, or roasted preparations. Intake of MEL rich dietary food is accompanied by an increase in MEL content in human serum. ²⁷⁰, reports the higher intake of MEL rich food in the mediterranean diet. Grape, wine, tomato, and olives are the major source of MEL rich diet in the mediterranean countries. The fact that MEL is amphipathic in nature results in its good target specificity in crossing blood and brain barriers. It can effectively reach the target sites in human organs. The authors²⁷⁰ state that the efficacy and benefits of MEL rich diet largely depends upon assortment of food, beverages, and their consumption. Food sources rich in free tryptophan content can be considered as a good option toward SER enhancement in brain.²⁷¹ The author focuses on the nonpharmacological method of increasing brain SER. According to ²⁷², the act of plant breeding should invariably focus on nutrient value of crops. The author²⁷¹ therefore summarizes that tryptophan rich plant products shall be beneficial in mental health of populations. Solanum tubersoum has been reported to contain catecholamines (dopamine, norepinephrine, and normetanephrine) with highest amount in leaves. The levels decreased in tubers during postharvest cold storage conditions. Musa cavendishii has been reported to possess high dopamine content (2.5–560 mg/100 g) in pulp and peels thus suggesting its dietary importance.⁹⁹ Recent review reported that different animal foods, fruits, edible plants, roots, and botanicals were reported to contain NTs.²⁶² Glutamic acid naturally occurs in foods with high protein content (for example, meats, seafood, stews, soups, and sauces).²⁷³ Seaweeds, cheeses, fish sauces, soy sauces, fermented beans, and Solanum lycopersicum L. (that is, tomato) showed high levels of free glutamic acid. Fruits of the Musa genus, such as bananas and plantains, and the Persea americana M. species (that is, avocado) were reported to contain high levels of dopamine.²⁷⁴ In particular, sprouts of Lupinus angustifolius L. (that is, lupine) ²⁷⁵, and other germinating edible beans, such as Glycine max L. (that is, soya bean), ²⁷⁶ common bean, and pea²⁷⁷ were reported to increase GABA content when compared to their raw beans.

An analysis of literature survey on neurotransmitters in plant signaling: recent trends through omics approach

The various citations obtained within the range of 2010–2020 (last decade) reveal significant increase in research reports which decipher the role of neurotransmitters in plant signaling and development. The rationale for the present review was to analyze and update our current understandings of the role of neurotransmitters in plant system. The literatures obtained therefore effectively summarize the evolutionary significance of various neurotransmitters found both in animal and plant systems. Among various reports retrieved from search database (google scholar) reports on melatonin have been represented with maximum citations of approximately 290. Citations from various other biomolecules and their aspects of investigation have been summarized in Table 5. The reports retrieved were mostly in the range of 2000–2020. However, certain pioneer findings and preliminary investigations of physiological phenomenon earlier to the year 2000 have also been mentioned. The recent trends observed among various reports include omic approach and knockout analysis of various genes regulated by the effect of exogenous application of various neurotransmitters. The quest for deciphering functional receptors of various neurotransmitters have lured plant physiologist to pursue further investigations. Thus the fact that various neurotransmitters function in mechanisms similar to phytohormones remains persuasive at this point of time.

Table 5.

Literature survey on neurotransmitters in plant signaling.

Neurotransmitters	Aspect of investigation	Approximate citations from research and review reports (2010–2020)
Acetylcholine	Growth and morphogenesis, tropic response, phytochrome signaling	10
Catecholamines	Growth and development, flowering	04
Dopamine	Ion transport, hormonal crosstalk, stress signaling	11
GABA	Ca129+-CaM signaling, carbon and nitrogen metabolism, NO and polyamine signaling, stress tolerance	55
Biogenic amines(histamine, putrescine, spermidine)	Biogenic defense, stress signaling, flowering	190
Glutamate	Ion channel functioning, heat tolerance, membrane hyper -polarization, regulation of root architecture	32
Serotonin	Long distance signaling, auxin-interaction, growth and morphogenesis, regulation of root architecture, biotic and abiotic stress	48
Melatonin	Transcriptomic, genomic and proteomic analysis of stress signaling, PIN protein regulation, hormonal crosstalk, ROS homeostasis, ion transport, flowering and fruit and seed development, embryogenesis	290

Various reports analyzed in the present review have been retrieved on the basis of various criteria of findings-namely quantitative and qualitative analysis of biomolecules in various plant systems, localization methods, growth, and morphogenesis (including flowering and embryogenesis), primary metabolism, root growth regulation, signaling crosstalk and stress acclimatization. The literatures have been mostly obtained by excluding repetitive reports deciphering similar mechanisms in different plant systems. The recent trends and future perspectives have been summarized in the following section.

Future perspectives

Although NTs have been identified in various plant species, many unresolved questions remain to be deciphered till date. Further investigations on NTs as growth modulator in plants are necessary. Perhaps, the relation between NTs and phytohormones will open up new perspectives in the possible role of NTs in plant morphogenesis, flowering, seed dormancy, and stress-amelioration. Application of NTs in pharmacology, medicine, agriculture, and plant acclimatization shall provide more potential benefits. Novel insights provide important evidence to further specify the nature of the binding sites and deciphering the role of GABA in plants. Apparently, more work remains to be done to elucidate the relationship between GABA and other signaling molecules. Considering the fact that GABA and dopamine are metabolically associated with one or more pathways in plants and it is important to imply transgenic approach for modulation of activity of these biomolecules. New insights for future strategies related to the modulation of plant morphogenesis, and evaluation of physiological changes associated with GABA need to be studied. The hormonal crosstalk events associated with acetylcholine remains to be elucidated. It is interesting that SER and MEL (that affect human brain function) also affect the growth and development of higher plants. Recent reports on plant signaling, communication pathways and responses to environment have formed analogies to human neuro-networks. Identification of receptors for the major NTs like SER, MEL, dopamine, and GABA will open new vistas in understanding the exact mechanism of their action. The ecological importance of NTs invariably provides new avenues to decipher signaling mechanisms between plant-pathogen or root-microbe signaling. Disease development and hypersensitive reactions followed by a plethora of signaling events can be better understood in terms of amine signaling. Pollen-stigma recognition for cross-pollination in crops often implies certain NTs for signaling events. Further elaborate research is necessary to unveil the possible role of neuroamines in pollen biology. Self-incompatibility of pollens, germination vigor, and allelopathy are some of the aspects which require more attention. Formulations of SER, MEL, and other associated biogenic amines can be potentially implied for improving stress amelioration during salinity. Considering the prevalence of salt-affected soil world-wide it is worthwhile to attempt production of salt-tolerant crops transgenic in amine metabolism. Identify the genes related to ACh-mediated system such as a putative ACh receptor gene in plants. MEL/SER and their implication in photosynthesis efficiency, CO₂ assimilation, the carbohydrates/lipid/nitrogen metabolisms, and osmoregulation aspects remain to be understood.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Abbreviations

NTs

Neurotransmitters

Ach

Acetyl choline

AChE

Acetylcholine esterase

GABA

γ -amino buteric acid

SER

Serotonin

MEL

Melatonin