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6-OHDA-Lesioned Adult Zebrafish as a Useful Parkinson’s Disease Model for Dopaminergic Neuroregeneration

Conventional mammalian models of neurodegeneration are often limited by futile axonogenesis with minimal functional recuperation of severed neurons. The emergence of zebrafish, a non-mammalian model with excellent neuroregenerative properties, may address these limitations. This study aimed to estab...

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Main Authors: Vijayanathan, Yuganthini, Lim, Fei Tieng, Lim, Siong Meng, Long, Chiau Ming, Tan, Maw Pin, Majeed, Abu Bakar Abdul, Ramasamy, Kalavathy
Format: Article
Published: Springer Verlag 2017
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R Medicine
Online Access:http://eprints.um.edu.my/22845/
https://doi.org/10.1007/s12640-017-9778-x
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spelling my.um.eprints.228452019-10-24T06:45:07Z http://eprints.um.edu.my/22845/ 6-OHDA-Lesioned Adult Zebrafish as a Useful Parkinson’s Disease Model for Dopaminergic Neuroregeneration Vijayanathan, Yuganthini Lim, Fei Tieng Lim, Siong Meng Long, Chiau Ming Tan, Maw Pin Majeed, Abu Bakar Abdul Ramasamy, Kalavathy R Medicine Conventional mammalian models of neurodegeneration are often limited by futile axonogenesis with minimal functional recuperation of severed neurons. The emergence of zebrafish, a non-mammalian model with excellent neuroregenerative properties, may address these limitations. This study aimed to establish an adult zebrafish-based, neurotoxin-induced Parkinson’s disease (PD) model and subsequently validate the regenerative capability of dopaminergic neurons (DpN). The DpN of adult male zebrafish (Danio rerio) were lesioned by microinjecting 6-hydroxydopamine (6-OHDA) neurotoxin (6.25, 12.5, 18.75, 25, 37.5, 50 and 100 mg/kg) into the ventral diencephalon (Dn). This was facilitated by an optimised protocol that utilised 1,1′-dioctadecyl-3,3,3′,3′-tetramethyl-indocarbocyanineperchlorate (DiI) dye to precisely identify the injection site. Immunostaining was utilised to identify the number of tyrosine hydroxylase immunoreactive (TH-ir) DpN in brain regions of interest (i.e. olfactory bulb, telencephalon, preoptic area, posterior tuberculum and hypothalamus). Open tank video recordings were performed for locomotor studies. The Dn was accessed by setting the injection angle of the microinjection capillary to 60° and injection depth to 1200 μm (from the exposed brain surface). 6-OHDA (25 mg/kg) successfully ablated >85% of the Dn DpN (preoptic area, posterior tuberculum and hypothalamus) whilst maintaining a 100% survival. Locomotor analysis of 5-min recordings revealed that 6-OHDA-lesioned adult zebrafish were significantly (p < 0.0001) reduced in speed (cm/s) and distance travelled (cm). Lesioned zebrafish showed full recovery of Dn DpN 30 days post-lesion. This study had successfully developed a stable 6-OHDA-induced PD zebrafish model using a straightforward and reproducible approach. Thus, this developed teleost model poses exceptional potentials to study DpN regeneration. Springer Verlag 2017 Article PeerReviewed Vijayanathan, Yuganthini and Lim, Fei Tieng and Lim, Siong Meng and Long, Chiau Ming and Tan, Maw Pin and Majeed, Abu Bakar Abdul and Ramasamy, Kalavathy (2017) 6-OHDA-Lesioned Adult Zebrafish as a Useful Parkinson’s Disease Model for Dopaminergic Neuroregeneration. Neurotoxicity Research, 32 (3). pp. 496-508. ISSN 1029-8428 https://doi.org/10.1007/s12640-017-9778-x doi:10.1007/s12640-017-9778-x
institution Universiti Malaya
building UM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaya
content_source UM Research Repository
url_provider http://eprints.um.edu.my/
topic R Medicine
spellingShingle R Medicine
Vijayanathan, Yuganthini
Lim, Fei Tieng
Lim, Siong Meng
Long, Chiau Ming
Tan, Maw Pin
Majeed, Abu Bakar Abdul
Ramasamy, Kalavathy
6-OHDA-Lesioned Adult Zebrafish as a Useful Parkinson’s Disease Model for Dopaminergic Neuroregeneration
description Conventional mammalian models of neurodegeneration are often limited by futile axonogenesis with minimal functional recuperation of severed neurons. The emergence of zebrafish, a non-mammalian model with excellent neuroregenerative properties, may address these limitations. This study aimed to establish an adult zebrafish-based, neurotoxin-induced Parkinson’s disease (PD) model and subsequently validate the regenerative capability of dopaminergic neurons (DpN). The DpN of adult male zebrafish (Danio rerio) were lesioned by microinjecting 6-hydroxydopamine (6-OHDA) neurotoxin (6.25, 12.5, 18.75, 25, 37.5, 50 and 100 mg/kg) into the ventral diencephalon (Dn). This was facilitated by an optimised protocol that utilised 1,1′-dioctadecyl-3,3,3′,3′-tetramethyl-indocarbocyanineperchlorate (DiI) dye to precisely identify the injection site. Immunostaining was utilised to identify the number of tyrosine hydroxylase immunoreactive (TH-ir) DpN in brain regions of interest (i.e. olfactory bulb, telencephalon, preoptic area, posterior tuberculum and hypothalamus). Open tank video recordings were performed for locomotor studies. The Dn was accessed by setting the injection angle of the microinjection capillary to 60° and injection depth to 1200 μm (from the exposed brain surface). 6-OHDA (25 mg/kg) successfully ablated >85% of the Dn DpN (preoptic area, posterior tuberculum and hypothalamus) whilst maintaining a 100% survival. Locomotor analysis of 5-min recordings revealed that 6-OHDA-lesioned adult zebrafish were significantly (p < 0.0001) reduced in speed (cm/s) and distance travelled (cm). Lesioned zebrafish showed full recovery of Dn DpN 30 days post-lesion. This study had successfully developed a stable 6-OHDA-induced PD zebrafish model using a straightforward and reproducible approach. Thus, this developed teleost model poses exceptional potentials to study DpN regeneration.
format Article
author Vijayanathan, Yuganthini
Lim, Fei Tieng
Lim, Siong Meng
Long, Chiau Ming
Tan, Maw Pin
Majeed, Abu Bakar Abdul
Ramasamy, Kalavathy
author_facet Vijayanathan, Yuganthini
Lim, Fei Tieng
Lim, Siong Meng
Long, Chiau Ming
Tan, Maw Pin
Majeed, Abu Bakar Abdul
Ramasamy, Kalavathy
author_sort Vijayanathan, Yuganthini
title 6-OHDA-Lesioned Adult Zebrafish as a Useful Parkinson’s Disease Model for Dopaminergic Neuroregeneration
title_short 6-OHDA-Lesioned Adult Zebrafish as a Useful Parkinson’s Disease Model for Dopaminergic Neuroregeneration
title_full 6-OHDA-Lesioned Adult Zebrafish as a Useful Parkinson’s Disease Model for Dopaminergic Neuroregeneration
title_fullStr 6-OHDA-Lesioned Adult Zebrafish as a Useful Parkinson’s Disease Model for Dopaminergic Neuroregeneration
title_full_unstemmed 6-OHDA-Lesioned Adult Zebrafish as a Useful Parkinson’s Disease Model for Dopaminergic Neuroregeneration
title_sort 6-ohda-lesioned adult zebrafish as a useful parkinson’s disease model for dopaminergic neuroregeneration
publisher Springer Verlag
publishDate 2017
url http://eprints.um.edu.my/22845/
https://doi.org/10.1007/s12640-017-9778-x
_version_ 1648736228774772736
score 13.211869

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