TABLE 2.

Summary of the physiological and behavioral effects observed on the neurotoxin-induced and transgenic zebrafish model of PD.

Environmental neurotoxin	Observed effects upon exposure on zebrafish		References
	Physiological effects	Behavioral effects
Neurotoxin-induced zebrafish model of PD
MPTP	– Perturbation of mitochondrial electron transport chain through binding with mitochondrial complex I – Reduced ATP production – Increased ROS production	– Motor impairments (reduced swimming speed, aberrant swimming behavior, increased time spent at the bottom of the tank, increased number of freezing bouts) – Weakened touch sensory (slow trunk and tail reflexes in response to the stimuli)	Lam et al., 2005; Zawada et al., 2011; Perier and Vila, 2012; Ketzef et al., 2017; Robea et al., 2020; Wasel and Freeman, 2020
6-OHDA	– Inhibition of the mitochondrial complex I activity – Increased ROS production – Reduced dopamine level – Activation of microglia-mediated neuroinflammation	– Motor impairments [reduced swimming speed, reduced distance traveled, reduced burst swimming (larval zebrafish)] – Anxiety (longer time spent at the lower part of the cuvette)	Carvalho et al., 2013; Bonito-Oliva et al., 2014; Feng et al., 2014; Makhija and Jagtap, 2014; Vijayanathan et al., 2017; Cobley et al., 2018; Vaz et al., 2020; Kesh et al., 2021
Paraquat	– Increased ROS production – Reduced ATP production – Activation of the TLR4/NFκB neuroinflammatory pathway – DNA fragmentation	– Motor impairments (reduced distance traveled, reduced swimming velocity, increased number of freezing bouts and freezing durations) – Impaired spatial memory – Anxiety – Aggression	Nunes et al., 2017; Wang et al., 2018; Bastías-Candia et al., 2019; Feng et al., 2019; Vaccari et al., 2019; Huang et al., 2020; Joseph et al., 2020
Rotenone	– Inhibition of the mitochondrial complex I activity – Increased ROS production – Reduced ATP production – α-synuclein aggregation – Reduced dopamine level – Reduced mitochondrial calcium level – Increased activation of microglia and pro-inflammatory proteins	– Motor impairments (reduced swimming speed, reduced distance traveled) – Anxiety – Depression – Olfactory dysfunction	Gao et al., 2013; Wang et al., 2017; Lv et al., 2019; Hijaz and Volpicelli-Daley, 2020; Ramli et al., 2020; Ünal et al., 2020; Yurtsever et al., 2020
PD-associated gene/Encoded protein	Observed effects of mutations on zebrafish		References
	Physiological effects	Behavioral effects
Transgenic zebrafish model of PD
SNCA/Synuclein	– Reduced dopamine level – Reduced mitochondrial activity – Increased ROS production	– Motor impairment (reduced spontaneous swimming behavior)	Milanese et al., 2012; O’Donnell et al., 2014; Grünewald et al., 2019; Robea et al., 2020
PARK2/Parkin	– Reduced mitochondrial activity – Reduced DA neuronal population – Increased susceptibility to toxic metabolites	– No significant swimming behavioral abnormality	Flinn et al., 2009; Vaz et al., 2018; Wasel and Freeman, 2020
PINK1/PINK1	– Mitochondrial dysfunction – Developmental retardation – Increased ROS production – Increased susceptibility to MPTP	– Motor impairment (abnormal swimming behavior) – Impaired response to tactile stimuli	Anichtchik et al., 2008; Sallinen et al., 2010; Xi et al., 2010; Priyadarshini et al., 2013
PARL/PARL	– Dysregulation of the PINK1/Parkin mitophagy pathway – Reduced DA neuronal population – Increased mortality	– Motor impairment (reduced distance traveled and swimming velocity, increased freezing bouts) – Olfactory dysfunction	Noble et al., 2012; Shamchuk et al., 2017; Merhi et al., 2021
PARK7/DJ-1	– Increased ROS production – Impaired mitophagy	– Motor impairment (reduced swimming velocity, increased freezing bouts)	Dolgacheva et al., 2019; Edson et al., 2019
LRRK2/LRRK2	– Neuronal cell loss – Synuclein aggregation – Heightened kinase activity – Weakened immunity toward bacterial infection	– Motor impairment (reduced swimming distance)	Sheng et al., 2010; Prabhudesai et al., 2016; Sheng et al., 2018; Seegobin et al., 2020