Table 1.
Summary of studies on brainstem nuclei along with their physiological and pathological roles (+ indicate increase and − is decrease in expression).
| Nucleus | Brain area | Role of nucleus | Neurotransmitter | Expression | Alteration in function | Possible cause | Reference |
|---|---|---|---|---|---|---|---|
| KFN | Rostral PONS, brainstem | Arousal/sleep breathing control in perinatal life, synaptic plasticity | OR, BDNF | − | Fetal inhibitory reflex arrest breathing, deranged normal KFN development, and loss of breathing control | Hypoxic conditions, smoking | (36, 37) |
| ICN | Mesencephalon | Acoustic processing | 5-HT | − | Dysgenesis of RN, superior ON, ICN | Nicotinic absorption, smoking | (26, 38) |
| Nucleolus | Brainstem | Ribosomal synthesis | AgNOR | − | PC degeneration, disturbed cardiac cycle | Nicotinic absorption, smoking | (39) |
| AP | Fourth ventricle | Controls vomiting | − | − | AP lesion | Insecticide | (40) |
| LC, KFN, CAN, RN, pre-BotC, PF/FC | Cerebral cortex | Breathing control, sleep–awake cycle | α7-NAcR | + | Hypoplasia of all nuclei | Smoking, insecticide | (14, 41) |
| POD | Cerebellar Purkinje | RR | α7-NAcR | Alterations of POD network | Smoking | (42) | |
| NN | Brainstem | Mitotic cycle | NeuN | − | Cell death increased, neuronal immaturity | Smoking | (43) |
| LC | Brainstem | Sleep–wake cycle, control of CRS | TK, NM, TH | − | NM, hypoplasia, neuronal death, alterations of noradrenaline system, low neuromelanin, neuronal death | Smoking | (44) |
| SOC | Brainstem | Acoustic information | − | − | Hypoplasia of ON, RTN, FN, hypercellularity, dysgenesis of structures related to RR, alterations in auditory, and respiratory network | Smoking | (26, 45) |
| RTN | Caudal pons | Breathing, chemoreception | PHOX2B | − | Developmental abnormalities in RTN | Smoking | (46) |
| AP | Brainstem, fourth ventricle choroid plexus | Autonomic control of cardiac and respiratory activity | − | − | Lack of vascularization, hypoplasia, cystic formations, reactive gliosis | Smoking | (47) |
| STrN | Brainstem | Pain, thermofluctuations, RR | SP | −+ | Pre-BtzC, RN, and AN hypoplasia | Smoking | (48) |
| IMN | Brainstem | Breathing activity | − | − | Hypoplasia, neuronal immaturity | Smoking | (49) |
| G-Mt | Brainstem | Modulation of spinal cord motor activity | − | − | Hypoplasia, apoptosis | Smoking | (50) |
| HGN | Brainstem | Swallowing, chewing, vocalization, inspiration | SM | + | Hypoplasia, hyperplasia, no interneurons | Smoking | (51) |
| RN | Brainstem | Sleep–wake cycle | 5-HTT | − | Hypoplasia | Smoking | (52) |
| Pre-BotC | Medulla | RR | NK1R, SM | − | Hypoplasia, low neuronal no., dendritic hypodevelopment | Smoking | (53) |
OR, orexin receptor; BDNF, brain-derived neurotrophic factor; 5-HT, serotonin; AP, area prostrema; RTN, retrotrapezoid nucleus; ON, olivary nucleus; LC, locus coerulius; STrN, spinal trigeminal nucleus; KFN, Kölliker–Fuse nucleus; ICN, inferior collicus nucleus; RN, raphe nucleus; AN, arcuate nucleus; PF/FC, parafacial/facial complex; pre-BotC, pre-Bötzinger; IMN, intermediolateral nucleus; G-Mt, Guillain–Mollaret triangle (dentato-rubro-olivary network); HGN, hypoglossal nucleus; α7-NacR, α7-nicotinic acetylcholine receptor; TK, tyrosine kinase; NM, neuromelanin; CRS, cardiorespiratory system; RR, respiratory rhythm; TH, tyrosine hydroxylase; NN, nucleus of neurons; POD, Purkinje-olivo-dentate network; SM, somatostatin; 5-HTT, serotonin transporter; NK1R, neurokinin 1 receptor.