In this work, we carried out neurochemical and behavioral analysis of zebrafish (Danio rerio) treated with rotenone, an agent used to chemically induce a syndrome resembling Parkinson's disease (PD). Dopamine release, measured with fast-scan cyclic voltammetry (FSCV) at carbon-fiber electrodes in acutely harvested whole brains, was about 30% of that found in controls. Uptake, represented by the first order rate constant (k) and the half-life (t1/2) determined by nonlinear regression modeling of the stimulated release plots, was also diminished. Behavioral analysis revealed that rotenone treatment increased the time required for zebrafish to reach a reward within a maze by more than 50% and caused fish to select the wrong pathway, suggesting that latent learning was impaired. Additionally, zebrafish treated with rotenone suffered from diminished locomotor activity, swimming shorter distances with lower mean velocity and acceleration. Thus, the neurochemical and behavioral approaches, as applied, were able to resolve rotenone-induced differences in key parameters. This approach may be effective for screening therapies in this and other models of neurodegeneration.

Department of Analytical Chemistry UNESCO Laboratory of Environmental Electrochemistry Charles University Prague 2 12843 Czech Republic

Department of Chemistry and R N Adams Institute for Bioanalytical Chemistry University of Kansas Lawrence Kansas 66045 United States

Zobrazit více v PubMed

Ng JSC, Palliative care for Parkinson’s disease. Ann Palliat Med 2018, 7 (3), 296–303. PubMed

Parent M; Parent A, Substantia nigra and Parkinson’s disease: a brief history of their long and intimate relationship. Can J Neurol Sci 2010, 37 (3), 313–9. PubMed

Hornykiewicz O, [Dopamine (3-hydroxytyramine) in the central nervous system and its relation to the Parkinson syndrome in man]. Dtsch Med Wochenschr 1962, 87, 1807–10. PubMed

Berardelli A; Rothwell JC; Thompson PD; Hallett M, Pathophysiology of bradykinesia in Parkinson’s disease. Brain 2001, 124 (Pt 11), 2131–46. PubMed

Sagar HJ; Sullivan EV; Gabrieli JD; Corkin S; Growdon JH, Temporal ordering and short-term memory deficits in Parkinson’s disease. Brain 1988, 111 ( Pt 3), 525–39. PubMed

Olson M; Lockhart TE; Lieberman A, Motor Learning Deficits in Parkinson’s Disease (PD) and Their Effect on Training Response in Gait and Balance: A Narrative Review. Front Neurol 2019, 10, 62. PubMed PMC

Anichtchik O; Diekmann H; Fleming A; Roach A; Goldsmith P; Rubinsztein DC, Loss of PINK1 function affects development and results in neurodegeneration in zebrafish. J Neurosci 2008, 28 (33), 8199–207. PubMed PMC

Cansiz D; Ustundag UV; Unal I; Alturfan AA; Emekli-Alturfan E, Morphine attenuates neurotoxic effects of MPTP in zebrafish embryos by regulating oxidant/antioxidant balance and acetylcholinesterase activity. Drug Chem Toxicol 2021, 1–9. PubMed

Diaz-Casado ME; Lima E; Garcia JA; Doerrier C; Aranda P; Sayed RK; Guerra-Librero A; Escames G; Lopez LC; Acuna-Castroviejo D, Melatonin rescues zebrafish embryos from the parkinsonian phenotype restoring the parkin/PINK1/DJ-1/MUL1 network. J Pineal Res 2016, 61 (1), 96–107. PubMed

Kalyn M; Ekker M, Cerebroventricular Microinjections of MPTP on Adult Zebrafish Induces Dopaminergic Neuronal Death, Mitochondrial Fragmentation, and Sensorimotor Impairments. Front Neurosci 2021, 15, 718244. PubMed PMC

Noble S; Ismail A; Godoy R; Xi Y; Ekker M, Zebrafish Parla- and Parlb-deficiency affects dopaminergic neuron patterning and embryonic survival. J Neurochem 2012, 122 (1), 196–207. PubMed

Priyadarshini M; Orosco LA; Panula PJ, Oxidative stress and regulation of Pink1 in zebrafish (Danio rerio). PLoS One 2013, 8 (11), e81851. PubMed PMC

Priyadarshini M; Tuimala J; Chen YC; Panula P, A zebrafish model of PINK1 deficiency reveals key pathway dysfunction including HIF signaling. Neurobiol Dis 2013, 54, 127–38. PubMed

Sallinen V; Kolehmainen J; Priyadarshini M; Toleikyte G; Chen YC; Panula P, Dopaminergic cell damage and vulnerability to MPTP in Pink1 knockdown zebrafish. Neurobiol Dis 2010, 40 (1), 93–101. PubMed

Soman S; Keatinge M; Moein M; Da Costa M; Mortiboys H; Skupin A; Sugunan S; Bazala M; Kuznicki J; Bandmann O, Inhibition of the mitochondrial calcium uniporter rescues dopaminergic neurons in pink1(−/−) zebrafish. Eur J Neurosci 2017, 45 (4), 528–535. PubMed PMC

Xi Y; Ryan J; Noble S; Yu M; Yilbas AE; Ekker M, Impaired dopaminergic neuron development and locomotor function in zebrafish with loss of pink1 function. Eur J Neurosci 2010, 31 (4), 623–33. PubMed

Flinn L; Mortiboys H; Volkmann K; Koster RW; Ingham PW; Bandmann O, Complex I deficiency and dopaminergic neuronal cell loss in parkin-deficient zebrafish (Danio rerio). Brain 2009, 132 (Pt 6), 1613–23. PubMed

Hu ZY; Chen B; Zhang JP; Ma YY, Up-regulation of autophagy-related gene 5 (ATG5) protects dopaminergic neurons in a zebrafish model of Parkinson’s disease. J Biol Chem 2017, 292 (44), 18062–18074. PubMed PMC

Mignani L; Zizioli D; Borsani G; Monti E; Finazzi D, The Downregulation of c19orf12 Negatively Affects Neuronal and Musculature Development in Zebrafish Embryos. Front Cell Dev Biol 2020, 8, 596069. PubMed PMC

Prabhudesai S; Bensabeur FZ; Abdullah R; Basak I; Baez S; Alves G; Holtzman NG; Larsen JP; Moller SG, LRRK2 knockdown in zebrafish causes developmental defects, neuronal loss, and synuclein aggregation. J Neurosci Res 2016, 94 (8), 717–35. PubMed

Sanchez E; Azcona LJ; Paisan-Ruiz C, Pla2g6 Deficiency in Zebrafish Leads to Dopaminergic Cell Death, Axonal Degeneration, Increased beta-Synuclein Expression, and Defects in Brain Functions and Pathways. Mol Neurobiol 2018, 55 (8), 6734–6754. PubMed

Son OL; Kim HT; Ji MH; Yoo KW; Rhee M; Kim CH, Cloning and expression analysis of a Parkinson’s disease gene, uch-L1, and its promoter in zebrafish. Biochem Biophys Res Commun 2003, 312 (3), 601–7. PubMed

Betarbet R; Sherer TB; MacKenzie G; Garcia-Osuna M; Panov AV; Greenamyre JT, Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat Neurosci 2000, 3 (12), 1301–6. PubMed

Benvenutti R; Marcon M; Reis CG; Nery LR; Miguel C; Herrmann AP; Vianna MRM; Piato A, N-acetylcysteine protects against motor, optomotor and morphological deficits induced by 6-OHDA in zebrafish larvae. PeerJ 2018, 6, e4957. PubMed PMC

Fiametti LO; Correa CN; Castro LM, Peptide Profile of Zebrafish Brain in a 6-OHDA-Induced Parkinson Model. Zebrafish 2021, 18 (1), 55–65. PubMed

Vijayanathan Y; Lim FT; Lim SM; Long CM; Tan MP; Majeed ABA; Ramasamy K, 6-OHDA-Lesioned Adult Zebrafish as a Useful Parkinson’s Disease Model for Dopaminergic Neuroregeneration. Neurotox Res 2017, 32 (3), 496–508. PubMed

Zhang C; Li C; Chen S; Li Z; Jia X; Wang K; Bao J; Liang Y; Wang X; Chen M; Li P; Su H; Wan JB; Lee SMY; Liu K; He C, Berberine protects against 6-OHDA-induced neurotoxicity in PC12 cells and zebrafish through hormetic mechanisms involving PI3K/AKT/Bcl-2 and Nrf2/HO-1 pathways. Redox Biol 2017, 11, 1–11. PubMed PMC

Zhang LQ; Sa F; Chong CM; Wang Y; Zhou ZY; Chang RC; Chan SW; Hoi PM; Yuen Lee SM, Schisantherin A protects against 6-OHDA-induced dopaminergic neuron damage in zebrafish and cytotoxicity in SH-SY5Y cells through the ROS/NO and AKT/GSK3beta pathways. J Ethnopharmacol 2015, 170, 8–15. PubMed

Bashirzade AAO; Cheresiz SV; Belova AS; Drobkov AV; Korotaeva AD; Azizi-Arani S; Azimirad A; Odle E; Gild EV; Ardashov OV; Volcho KP; Bozhko DV; Myrov VO; Kolchanova SM; Polovian AI; Galumov GK; Salakhutdinov NF; Amstislavskaya TG; Kalueff AV, MPTP-Treated Zebrafish Recapitulate ‘Late-Stage’ Parkinson’s-like Cognitive Decline. Toxics 2022, 10 (2). PubMed PMC

Lam CS; Korzh V; Strahle U, Zebrafish embryos are susceptible to the dopaminergic neurotoxin MPTP. Eur J Neurosci 2005, 21 (6), 1758–62. PubMed

Li X; Gao D; Paudel YN; Li X; Zheng M; Liu G; Ma Y; Chu L; He F; Jin M, Anti-Parkinson’s Disease Activity of Sanghuangprous vaninii Extracts in the MPTP-Induced Zebrafish Model. ACS Chem Neurosci 2022, 13 (3), 330–339. PubMed

McKinley ET; Baranowski TC; Blavo DO; Cato C; Doan TN; Rubinstein AL, Neuroprotection of MPTP-induced toxicity in zebrafish dopaminergic neurons. Brain Res Mol Brain Res 2005, 141 (2), 128–37. PubMed

Sallinen V; Torkko V; Sundvik M; Reenila I; Khrustalyov D; Kaslin J; Panula P, MPTP and MPP+ target specific aminergic cell populations in larval zebrafish. J Neurochem 2009, 108 (3), 719–31. PubMed

Wen L; Wei W; Gu W; Huang P; Ren X; Zhang Z; Zhu Z; Lin S; Zhang B, Visualization of monoaminergic neurons and neurotoxicity of MPTP in live transgenic zebrafish. Dev Biol 2008, 314 (1), 84–92. PubMed

Anand SK; Sahu MR; Mondal AC, Bacopaside-I Alleviates the Detrimental Effects of Acute Paraquat Intoxication in the Adult Zebrafish Brain. Neurochem Res 2021, 46 (11), 3059–3074. PubMed

Bortolotto JW; Cognato GP; Christoff RR; Roesler LN; Leite CE; Kist LW; Bogo MR; Vianna MR; Bonan CD, Long-term exposure to paraquat alters behavioral parameters and dopamine levels in adult zebrafish (Danio rerio). Zebrafish 2014, 11 (2), 142–53. PubMed

Feng N; Bian Z; Zhang X; Wang C; Chen J, Rapamycin reduces mortality in acute-stage paraquat-induced toxicity in zebrafish. Singapore Med J 2019, 60 (5), 241–246. PubMed PMC

Joseph TP; Jagadeesan N; Sai LY; Lin SL; Sahu S; Schachner M, Adhesion Molecule L1 Agonist Mimetics Protect Against the Pesticide Paraquat-Induced Locomotor Deficits and Biochemical Alterations in Zebrafish. Front Neurosci 2020, 14, 458. PubMed PMC

Ling LB; Chang Y; Liu CW; Lai PL; Hsu T, Oxidative stress intensity-related effects of cadmium (Cd) and paraquat (PQ) on UV-damaged-DNA binding and excision repair activities in zebrafish (Danio rerio) embryos. Chemosphere 2017, 167, 10–18. PubMed

Liu H; Wu Q; Chu T; Mo Y; Cai S; Chen M; Zhu G, High-dose acute exposure of paraquat induces injuries of swim bladder, gastrointestinal tract and liver via neutrophil-mediated ROS in zebrafish and their relevance for human health risk assessment. Chemosphere 2018, 205, 662–673. PubMed

Mohamad Najib NH; Yahaya MF; Das S; Teoh SL, The effects of metallothionein in paraquat-induced Parkinson disease model of zebrafish. Int J Neurosci 2021, 1–12. PubMed

Muller TE; Nunes ME; Menezes CC; Marins AT; Leitemperger J; Gressler ACL; Carvalho FB; de Freitas CM; Quadros VA; Fachinetto R; Rosemberg DB; Loro VL, Sodium Selenite Prevents Paraquat-Induced Neurotoxicity in Zebrafish. Mol Neurobiol 2018, 55 (3), 1928–1941. PubMed

Nellore J; P N, Paraquat exposure induces behavioral deficits in larval zebrafish during the window of dopamine neurogenesis. Toxicol Rep 2015, 2, 950–956. PubMed PMC

Nunes ME; Muller TE; Braga MM; Fontana BD; Quadros VA; Marins A; Rodrigues C; Menezes C; Rosemberg DB; Loro VL, Chronic Treatment with Paraquat Induces Brain Injury, Changes in Antioxidant Defenses System, and Modulates Behavioral Functions in Zebrafish. Mol Neurobiol 2017, 54 (6), 3925–3934. PubMed

Wang Q; Liu S; Hu D; Wang Z; Wang L; Wu T; Wu Z; Mohan C; Peng A, Identification of apoptosis and macrophage migration events in paraquat-induced oxidative stress using a zebrafish model. Life Sci 2016, 157, 116–124. PubMed

Wang XH; Souders CL 2nd; Zhao YH; Martyniuk CJ, Paraquat affects mitochondrial bioenergetics, dopamine system expression, and locomotor activity in zebrafish (Danio rerio). Chemosphere 2018, 191, 106–117. PubMed

Cansiz D; Unal I; Ustundag UV; Alturfan AA; Altinoz MA; Elmaci I; Emekli-Alturfan E, Caprylic acid ameliorates rotenone induced inflammation and oxidative stress in the gut-brain axis in Zebrafish. Mol Biol Rep 2021, 48 (6), 5259–5273. PubMed

Ilie OD; Paduraru E; Robea MA; Balmus IM; Jijie R; Nicoara M; Ciobica A; Nita IB; Dobrin R; Doroftei B, The Possible Role of Bifidobacterium longum BB536 and Lactobacillus rhamnosus HN001 on Locomotor Activity and Oxidative Stress in a Rotenone-Induced Zebrafish Model of Parkinson’s Disease. Oxid Med Cell Longev 2021, 2021, 9629102. PubMed PMC

Lv DJ; Li LX; Chen J; Wei SZ; Wang F; Hu H; Xie AM; Liu CF, Sleep deprivation caused a memory defects and emotional changes in a rotenone-based zebrafish model of Parkinson’s disease. Behav Brain Res 2019, 372, 112031. PubMed

Surmen MG; Surmen S; Cansiz D; Unal I; Ustundag UV; Alturfan AA; Buyukkayhan D; Emekli-Alturfan E, Amelioration of rotenone-induced alterations in energy/redox system, stress response and cytoskeleton proteins by octanoic acid in zebrafish: A proteomic study. J Biochem Mol Toxicol 2022, e23024. PubMed

Surmen MG; Surmen S; Cansiz D; Unal I; Ustundag UV; Alturfan AA; Emekli-Alturfan E, Quantitative phosphoproteomics to resolve the cellular responses to octanoic acid in rotenone exposed zebrafish. J Food Biochem 2021, 45 (10), e13923. PubMed

Unal I; Ustundag UV; Ates PS; Egilmezer G; Alturfan AA; Yigitbasi T; Emekli-Alturfan E, Rotenone impairs oxidant/antioxidant balance both in brain and intestines in zebrafish. Int J Neurosci 2019, 129 (4), 363–368. PubMed

Ustundag FD; Unal I; Ustundag UV; Cansiz D; Beler M; Karagoz A; Kara Subasat H; Alturfan AA; Mega Tiber P; Emekli-Alturfan E, 3-Pyridinylboronic Acid Ameliorates Rotenone-Induced Oxidative Stress Through Nrf2 Target Genes in Zebrafish Embryos. Neurochem Res 2022. PubMed

Wang Y; Liu W; Yang J; Wang F; Sima Y; Zhong ZM; Wang H; Hu LF; Liu CF, Parkinson’s disease-like motor and non-motor symptoms in rotenone-treated zebrafish. Neurotoxicology 2017, 58, 103–109. PubMed

Yurtsever I; Ustundag UV; Unal I; Ates PS; Emekli-Alturfan E, Rifampicin decreases neuroinflammation to maintain mitochondrial function and calcium homeostasis in rotenone-treated zebrafish. Drug Chem Toxicol 2020, 1–8. PubMed

Fulks JL; O’Bryhim BE; Wenzel SK; Fowler SC; Vorontsova E; Pinkston JW; Ortiz AN; Johnson MA, Dopamine Release and Uptake Impairments and Behavioral Alterations Observed in Mice that Model Fragile X Mental Retardation Syndrome. ACS Chem Neurosci 2010, 1 (10), 679–690. PubMed PMC

Ortiz AN; Kurth BJ; Osterhaus GL; Johnson MA, Impaired dopamine release and uptake in R6/1 Huntington’s disease model mice. Neurosci Lett 2011, 492 (1), 11–4. PubMed PMC

Ortiz AN; Oien DB; Moskovitz J; Johnson MA, Quantification of reserve pool dopamine in methionine sulfoxide reductase A null mice. Neuroscience 2011, 177, 223–9. PubMed PMC

Jarmolowicz DP; Gehringer R; Lemley SM; Sofis MJ; Kaplan S; Johnson MA, 5-Fluorouracil impairs attention and dopamine release in rats. Behav Brain Res 2019, 362, 319–322. PubMed PMC

Kaplan SV; Limbocker RA; Gehringer RC; Divis JL; Osterhaus GL; Newby MD; Sofis MJ; Jarmolowicz DP; Newman BD; Mathews TA; Johnson MA, Impaired Brain Dopamine and Serotonin Release and Uptake in Wistar Rats Following Treatment with Carboplatin. ACS Chem Neurosci 2016, 7 (6), 689–99. PubMed PMC

Kraft JC; Osterhaus GL; Ortiz AN; Garris PA; Johnson MA, In vivo dopamine release and uptake impairments in rats treated with 3-nitropropionic acid. Neuroscience 2009, 161 (3), 940–9. PubMed

Ortiz AN; Osterhaus GL; Lauderdale K; Mahoney L; Fowler SC; von Horsten S; Riess O; Johnson MA, Motor function and dopamine release measurements in transgenic Huntington’s disease model rats. Brain Res 2012, 1450, 148–56. PubMed PMC

Field TM; Shin M; Stucky CS; Loomis J; Johnson MA, Electrochemical Measurement of Dopamine Release and Uptake in Zebrafish Following Treatment with Carboplatin. Chemphyschem 2018, 19 (10), 1192–1196. PubMed PMC

Jarosova R; Douglass AD; Johnson MA, Optimized Sawhorse Waveform for the Measurement of Oxytocin Release in Zebrafish. Anal Chem 2022, 94 (6), 2942–2949. PubMed PMC

Shin M; Field TM; Stucky CS; Furgurson MN; Johnson MA, Ex Vivo Measurement of Electrically Evoked Dopamine Release in Zebrafish Whole Brain. ACS Chem Neurosci 2017, 8 (9), 1880–1888. PubMed PMC

Jones LJ; McCutcheon JE; Young AM; Norton WH, Neurochemical measurements in the zebrafish brain. Front Behav Neurosci 2015, 9, 246. PubMed PMC

Shang CF; Li XQ; Yin C; Liu B; Wang YF; Zhou Z; Du JL, Amperometric Monitoring of Sensory-Evoked Dopamine Release in Awake Larval Zebrafish. J Neurosci 2015, 35 (46), 15291–4. PubMed PMC

Benvenutti R; Marcon M; Gallas-Lopes M; de Mello AJ; Herrmann AP; Piato A, Swimming in the maze: An overview of maze apparatuses and protocols to assess zebrafish behavior. Neurosci Biobehav Rev 2021, 127, 761–778. PubMed

Wade C; Tavris C, Psychology in Perspective. 2nd ed.; Longman: New York, 1997.

Gómez-Laplaza LM; Gerlai R, Latent learning in zebrafish (Danio rerio). Behav Brain Res 2010, 208 (2), 509–515. PubMed PMC

Luchiari AC; Salajan DC; Gerlai R, Acute and chronic alcohol administration: effects on performance of zebrafish in a latent learning task. Behav Brain Res 2015, 282, 76–83. PubMed PMC

Naderi M; Salahinejad A; Jamwal A; Chivers DP; Niyogi S, Chronic Dietary Selenomethionine Exposure Induces Oxidative Stress, Dopaminergic Dysfunction, and Cognitive Impairment in Adult Zebrafish (Danio rerio). Environ Sci Technol 2017, 51 (21), 12879–12888. PubMed

Naderi M; Jamwal A; Ferrari MC; Niyogi S; Chivers DP, Dopamine receptors participate in acquisition and consolidation of latent learning of spatial information in zebrafish (Danio rerio). Prog Neuropsychopharmacol Biol Psychiatry 2016, 67, 21–30. PubMed

Maegawa H; Niwa H, Generation of Mitochondrial Toxin Rodent Models of Parkinson’s Disease Using 6-OHDA , MPTP , and Rotenone. Methods Mol Biol 2021, 2322, 95–110. PubMed

Rink E; Wullimann MF, The teleostean (zebrafish) dopaminergic system ascending to the subpallium (striatum) is located in the basal diencephalon (posterior tuberculum). Brain Research 2001, 889 (1), 316–330. PubMed

Lotharius J; Brundin P, Pathogenesis of parkinson’s disease: dopamine, vesicles and α-synuclein. Nature Reviews Neuroscience 2002, 3 (12), 932–942. PubMed

Yavich L; Oksman M; Tanila H; Kerokoski P; Hiltunen M; van Groen T; Puolivali J; Mannisto PT; Garcia-Horsman A; MacDonald E; Beyreuther K; Hartmann T; Jakala P, Locomotor activity and evoked dopamine release are reduced in mice overexpressing A30P-mutated human alpha-synuclein. Neurobiol Dis 2005, 20 (2), 303–13. PubMed

Bergstrom BP; Sanberg SG; Andersson M; Mithyantha J; Carroll FI; Garris PA, Functional reorganization of the presynaptic dopaminergic terminal in parkinsonism. Neuroscience 2011, 193, 310–22. PubMed PMC

Garris PA; Walker QD; Wightman RM, Dopamine release and uptake rates both decrease in the partially denervated striatum in proportion to the loss of dopamine terminals. Brain Res 1997, 753 (2), 225–34. PubMed

Liu B; Xie J, Increased dopamine release in vivo by estradiol benzoate from the central amygdaloid nucleus of Parkinson’s disease model rats. J Neurochem 2004, 90 (3), 654–8. PubMed

Wesemann W; Grote C; Clement HW; Block F; Sontag KH, Functional studies on monoaminergic transmitter release in parkinsonism. Prog Neuropsychopharmacol Biol Psychiatry 1993, 17 (3), 487–99. PubMed

Lin CH; Huang JY; Ching CH; Chuang JI, Melatonin reduces the neuronal loss, downregulation of dopamine transporter, and upregulation of D2 receptor in rotenone-induced parkinsonian rats. J Pineal Res 2008, 44 (2), 205–13. PubMed

Milusheva E; Baranyi M; Kormos E; Hracsko Z; Sylvester Vizi E; Sperlagh B, The effect of antiparkinsonian drugs on oxidative stress induced pathological [3H]dopamine efflux after in vitro rotenone exposure in rat striatal slices. Neuropharmacology 2010, 58 (4–5), 816–25. PubMed

Tien LT; Kaizaki A; Pang Y; Cai Z; Bhatt AJ; Fan LW, Neonatal exposure to lipopolysaccharide enhances accumulation of alpha-synuclein aggregation and dopamine transporter protein expression in the substantia nigra in responses to rotenone challenge in later life. Toxicology 2013, 308, 96–103. PubMed PMC

Creed RB; Goldberg MS, New Developments in Genetic rat models of Parkinson’s Disease. Movement Disorders 2018, 33 (5), 717–729. PubMed PMC

Ungerstedt U, 6-Hydroxy-dopamine induced degeneration of central monoamine neurons. Eur J Pharmacol 1968, 5 (1), 107–10. PubMed

Burns RS; Chiueh CC; Markey SP; Ebert MH; Jacobowitz DM; Kopin IJ, A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Proc Natl Acad Sci U S A 1983, 80 (14), 4546–50. PubMed PMC

Sawamoto N; Piccini P; Hotton G; Pavese N; Thielemans K; Brooks DJ, Cognitive deficits and striato-frontal dopamine release in Parkinson’s disease. Brain 2008, 131 (5), 1294–1302. PubMed

Mazzoni P; Shabbott B; Cortés JC, Motor control abnormalities in Parkinson’s disease. Cold Spring Harb Perspect Med 2012, 2 (6), a009282–a009282. PubMed PMC

Sabbagh MN; Adler CH; Lahti TJ; Connor DJ; Vedders L; Peterson LK; Caviness JN; Shill HA; Sue LI; Ziabreva I; Perry E; Ballard CG; Aarsland D; Walker DG; Beach TG, Parkinson disease with dementia: comparing patients with and without Alzheimer pathology. Alzheimer Dis Assoc Disord 2009, 23 (3), 295–297. PubMed PMC

Watson GS; Leverenz JB, Profile of Cognitive Impairment in Parkinson’s Disease. Brain Pathology 2010, 20 (3), 640–645. PubMed PMC

Bird CM; Burgess N, The hippocampus and memory: insights from spatial processing. Nature Reviews Neuroscience 2008, 9 (3), 182–194. PubMed

Roberts A; Bill B; Glanzman D, Learning and memory in zebrafish larvae. Frontiers in Neural Circuits 2013, 7. PubMed PMC

Levin ED; Chen E, Nicotinic involvement in memory function in zebrafish. Neurotoxicology and Teratology 2004, 26 (6), 731–735. PubMed

Bailey JM; Oliveri AN; Levin ED, Pharmacological analyses of learning and memory in zebrafish (Danio rerio). Pharmacology Biochemistry and Behavior 2015, 139, 103–111. PubMed PMC

Ichihara K, [Experimental techniques for developing new drugs acting on dementia (7)--A water-finding task for use with mice: utility for evaluating latent learning]. Nihon Shinkei Seishin Yakurigaku Zasshi 1994, 14 (5), 315–322. PubMed

Noda Y; Mamiya T; Manabe T; Nishi M; Takeshima H; Nabeshima T, Role of nociceptin systems in learning and memory. Peptides 2000, 21 (7), 1063–1069. PubMed

Flint RW; Valentine S; Papandrea D, Reconsolidation of a long-term spatial memory is impaired by cycloheximide when reactivated with a contextual latent learning trial in male and female rats. Neuroscience 2007, 148 (4), 833–844. PubMed

Stouffer EM; Heisey JL, Latent learning of spatial information is impaired in middle-aged rats. Dev Psychobiol 2013, 55 (3), 309–15. PubMed

Zhou T; Thung K-H; Liu M; Shi F; Zhang C; Shen D, Multi-modal latent space inducing ensemble SVM classifier for early dementia diagnosis with neuroimaging data. Medical Image Analysis 2020, 60, 101630. PubMed PMC

Facciol A; Gerlai R, Zebrafish Shoaling, Its Behavioral and Neurobiological Mechanisms, and Its Alteration by Embryonic Alcohol Exposure: A Review. Front Behav Neurosci 2020, 14, 572175. PubMed PMC

Planas-Ballve A; Vilas D, Cognitive Impairment in Genetic Parkinson’s Disease. Parkinsons Dis 2021, 2021, 8610285. PubMed PMC

Severiano ESC; Alarcao J; Pavao Martins I; Ferreira JJ, Frequency of dementia in Parkinson’s disease: A systematic review and meta-analysis. J Neurol Sci 2022, 432, 120077. PubMed