MPTP-Treated Zebrafish Recapitulate 'Late-Stage' Parkinson's-like Cognitive Decline

Alim A.O. Bashirzade; Sergey V. Cheresiz; Alisa S. Belova; Alexey V. Drobkov; Anastasiia D. Korotaeva; Soheil Azizi-Arani; Amirhossein Azimirad; Eric Odle; Emma Yanina V. Gild; Oleg V. Ardashov; Konstantin P. Volcho; Dmitrii V. Bozhko; Vladislav O. Myrov; Sofia M. Kolchanova; Aleksander I. Polovian; Georgii K. Galumov; Nariman F. Salakhutdinov; Tamara G. Amstislavskaya; Allan V. Kalueff

doi:10.3390/toxics10020069

MPTP-Treated Zebrafish Recapitulate 'Late-Stage' Parkinson's-like Cognitive Decline

Alim A.O. Bashirzade^*, Sergey V. Cheresiz, Alisa S. Belova, Alexey V. Drobkov, Anastasiia D. Korotaeva, Soheil Azizi-Arani, Amirhossein Azimirad, Eric Odle, Emma Yanina V. Gild, Oleg V. Ardashov, Konstantin P. Volcho, Dmitrii V. Bozhko, Vladislav O. Myrov, Sofia M. Kolchanova, Aleksander I. Polovian, Georgii K. Galumov, Nariman F. Salakhutdinov, Tamara G. Amstislavskaya, Allan V. Kalueff^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

13 Citations (Scopus)

Abstract

The zebrafish is a promising model species in biomedical research, including neurotoxicology and neuroactive drug screening. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) evokes degeneration of dopaminergic neurons and is commonly used to model Parkinson’s disease (PD) in laboratory animals, including zebrafish. However, cognitive phenotypes in MPTP-evoked experimental PD models remain poorly understood. Here, we established an LD50 (292 mg/kg) for intraperitoneal MPTP administration in adult zebrafish, and report impaired spatial working memory (poorer spontaneous alternation in the Y-maze) in a PD model utilizing fish treated with 200 µg of this agent. In addition to conventional behavioral analyses, we also employed artificial intelligence (AI)-based approaches to independently and without bias characterize MPTP effects on zebrafish behavior during the Y-maze test. These analyses yielded a distinct cluster for 200-µg MPTP (vs. other) groups, suggesting that high-dose MPTP produced distinct, computationally detectable patterns of zebrafish swimming. Collectively, these findings support MPTP treatment in adult zebrafish as a late-stage experimental PD model with overt cognitive phenotypes.

Original language	English
Article number	69
Journal	Toxics
Volume	10
Issue number	2
DOIs	https://doi.org/10.3390/toxics10020069
Publication status	Published - 4 Feb 2022
Externally published	Yes

Keywords

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
Artificial intelligence
Inhibitory avoidance task
Parkinson’s disease
Spontaneous alternation
Zebrafish

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10.3390/toxics10020069

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Bashirzade, A. A. O., Cheresiz, S. V., Belova, A. S., Drobkov, A. V., Korotaeva, A. D., Azizi-Arani, S., Azimirad, A., Odle, E., Gild, E. Y. V., Ardashov, O. V., Volcho, K. P., Bozhko, D. V., Myrov, V. O., Kolchanova, S. M., Polovian, A. I., Galumov, G. K., Salakhutdinov, N. F., Amstislavskaya, T. G., & Kalueff, A. V. (2022). MPTP-Treated Zebrafish Recapitulate 'Late-Stage' Parkinson's-like Cognitive Decline. Toxics, 10(2), Article 69. https://doi.org/10.3390/toxics10020069

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title = "MPTP-Treated Zebrafish Recapitulate 'Late-Stage' Parkinson's-like Cognitive Decline",

abstract = "The zebrafish is a promising model species in biomedical research, including neurotoxicology and neuroactive drug screening. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) evokes degeneration of dopaminergic neurons and is commonly used to model Parkinson{\textquoteright}s disease (PD) in laboratory animals, including zebrafish. However, cognitive phenotypes in MPTP-evoked experimental PD models remain poorly understood. Here, we established an LD50 (292 mg/kg) for intraperitoneal MPTP administration in adult zebrafish, and report impaired spatial working memory (poorer spontaneous alternation in the Y-maze) in a PD model utilizing fish treated with 200 µg of this agent. In addition to conventional behavioral analyses, we also employed artificial intelligence (AI)-based approaches to independently and without bias characterize MPTP effects on zebrafish behavior during the Y-maze test. These analyses yielded a distinct cluster for 200-µg MPTP (vs. other) groups, suggesting that high-dose MPTP produced distinct, computationally detectable patterns of zebrafish swimming. Collectively, these findings support MPTP treatment in adult zebrafish as a late-stage experimental PD model with overt cognitive phenotypes.",

keywords = "1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), Artificial intelligence, Inhibitory avoidance task, Parkinson{\textquoteright}s disease, Spontaneous alternation, Zebrafish",

author = "Bashirzade, {Alim A.O.} and Cheresiz, {Sergey V.} and Belova, {Alisa S.} and Drobkov, {Alexey V.} and Korotaeva, {Anastasiia D.} and Soheil Azizi-Arani and Amirhossein Azimirad and Eric Odle and Gild, {Emma Yanina V.} and Ardashov, {Oleg V.} and Volcho, {Konstantin P.} and Bozhko, {Dmitrii V.} and Myrov, {Vladislav O.} and Kolchanova, {Sofia M.} and Polovian, {Aleksander I.} and Galumov, {Georgii K.} and Salakhutdinov, {Nariman F.} and Amstislavskaya, {Tamara G.} and Kalueff, {Allan V.}",

note = "Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2022",

month = feb,

day = "4",

doi = "10.3390/toxics10020069",

language = "English",

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Bashirzade, AAO, Cheresiz, SV, Belova, AS, Drobkov, AV, Korotaeva, AD, Azizi-Arani, S, Azimirad, A, Odle, E, Gild, EYV, Ardashov, OV, Volcho, KP, Bozhko, DV, Myrov, VO, Kolchanova, SM, Polovian, AI, Galumov, GK, Salakhutdinov, NF, Amstislavskaya, TG & Kalueff, AV 2022, 'MPTP-Treated Zebrafish Recapitulate 'Late-Stage' Parkinson's-like Cognitive Decline', Toxics, vol. 10, no. 2, 69. https://doi.org/10.3390/toxics10020069

TY - JOUR

T1 - MPTP-Treated Zebrafish Recapitulate 'Late-Stage' Parkinson's-like Cognitive Decline

AU - Bashirzade, Alim A.O.

AU - Cheresiz, Sergey V.

AU - Belova, Alisa S.

AU - Drobkov, Alexey V.

AU - Korotaeva, Anastasiia D.

AU - Azizi-Arani, Soheil

AU - Azimirad, Amirhossein

AU - Odle, Eric

AU - Gild, Emma Yanina V.

AU - Ardashov, Oleg V.

AU - Volcho, Konstantin P.

AU - Bozhko, Dmitrii V.

AU - Myrov, Vladislav O.

AU - Kolchanova, Sofia M.

AU - Polovian, Aleksander I.

AU - Galumov, Georgii K.

AU - Salakhutdinov, Nariman F.

AU - Amstislavskaya, Tamara G.

AU - Kalueff, Allan V.

PY - 2022/2/4

Y1 - 2022/2/4

N2 - The zebrafish is a promising model species in biomedical research, including neurotoxicology and neuroactive drug screening. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) evokes degeneration of dopaminergic neurons and is commonly used to model Parkinson’s disease (PD) in laboratory animals, including zebrafish. However, cognitive phenotypes in MPTP-evoked experimental PD models remain poorly understood. Here, we established an LD50 (292 mg/kg) for intraperitoneal MPTP administration in adult zebrafish, and report impaired spatial working memory (poorer spontaneous alternation in the Y-maze) in a PD model utilizing fish treated with 200 µg of this agent. In addition to conventional behavioral analyses, we also employed artificial intelligence (AI)-based approaches to independently and without bias characterize MPTP effects on zebrafish behavior during the Y-maze test. These analyses yielded a distinct cluster for 200-µg MPTP (vs. other) groups, suggesting that high-dose MPTP produced distinct, computationally detectable patterns of zebrafish swimming. Collectively, these findings support MPTP treatment in adult zebrafish as a late-stage experimental PD model with overt cognitive phenotypes.

AB - The zebrafish is a promising model species in biomedical research, including neurotoxicology and neuroactive drug screening. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) evokes degeneration of dopaminergic neurons and is commonly used to model Parkinson’s disease (PD) in laboratory animals, including zebrafish. However, cognitive phenotypes in MPTP-evoked experimental PD models remain poorly understood. Here, we established an LD50 (292 mg/kg) for intraperitoneal MPTP administration in adult zebrafish, and report impaired spatial working memory (poorer spontaneous alternation in the Y-maze) in a PD model utilizing fish treated with 200 µg of this agent. In addition to conventional behavioral analyses, we also employed artificial intelligence (AI)-based approaches to independently and without bias characterize MPTP effects on zebrafish behavior during the Y-maze test. These analyses yielded a distinct cluster for 200-µg MPTP (vs. other) groups, suggesting that high-dose MPTP produced distinct, computationally detectable patterns of zebrafish swimming. Collectively, these findings support MPTP treatment in adult zebrafish as a late-stage experimental PD model with overt cognitive phenotypes.

KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)

KW - Artificial intelligence

KW - Inhibitory avoidance task

KW - Parkinson’s disease

KW - Spontaneous alternation

KW - Zebrafish

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U2 - 10.3390/toxics10020069

DO - 10.3390/toxics10020069

M3 - Article

AN - SCOPUS:85124333068

SN - 2305-6304

VL - 10

JO - Toxics

JF - Toxics

IS - 2

M1 - 69

ER -

MPTP-Treated Zebrafish Recapitulate 'Late-Stage' Parkinson's-like Cognitive Decline

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Keywords

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