Newly regenerated dopaminergic neurons in 6-OHDA-lesioned adult zebrafish brain proliferate in the Olfactory bulb and telencephalon, but migrate to, differentiate and mature in the diencephalon

Vijayanathan, Yuganthini and Hamzah, Naemah Md and Lim, Siong Meng and Lim, Fei Ting and Tan, Maw Pin and Majeed, Abu Bakar Abdul and Ramasamy, Kalavathy (2022) Newly regenerated dopaminergic neurons in 6-OHDA-lesioned adult zebrafish brain proliferate in the Olfactory bulb and telencephalon, but migrate to, differentiate and mature in the diencephalon. BRAIN RESEARCH BULLETIN, 190. pp. 218-233. ISSN 1873-2747, DOI https://doi.org/10.1016/j.brainresbull.2022.10.001.

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Official URL: https://doi.org/10.1016/j.brainresbull.2022.10.001

Abstract

In order to understand the biological processes underlying dopaminergic neurons (DpN) regeneration in a 6-hydroxydopamine(6-OHDA)-induced adult zebrafish-based Parkinson's disease model, this study investigated the specific phases of neuroregeneration in a time-based manner. Bromodeoxyuridine (BrdU) was administered 24 h before the harvest of brain tissues at day three, five, seven, nine, 12 and 14 postlesion. Potential migration of proliferative cells was tracked over 14 days postlesion through double-pulse tracking BrdU and 5-ethynyl-2 & PRIME;- deoxyuridine (EdU)] of cells and immunohistostaining of astrocytes glial fibrillary acidic protein (GFAP)]. Gene expression of foxa2 and nurr1 (nr4a2a) at day three, nine, 14, 18, 22 and 30 postlesion was quantified using qPCR. Protein expression of foxa2 at day three, seven, 14 and 22 postlesion was validated using the western blot technique. Double labelling EdU and tyrosine hydroxylase (TH)] of proliferative cells was performed to ascertain their fate after the neuroregeneration processes. It was found that whilst cell proliferation remained unchanged in the area of substantial DpN loss, the ventral diencephalon (vDn), there was a transient increase of cell proliferation in the olfactory bulb (OB) and telencephalon (Tel) seven days postlesion. BrdU-immunoreactive (ir)/ EdU-ir cells and activated astrocytes were later found to be significantly increased in the vDn and its nearby area (Tel) 14 days postlesion. There was a significant but transient downregulation of foxa2 at day three and nine postlesion, and nr4a2a at day three, nine and 14 postlesion. The expression of both genes remained unchanged in the OB and Tel. There was a transient downregulation of foxa2 protein expression at day three and seven postlesion. The significant increase of EdU-ir/ TH-ir cells in the vDn 30 days postlesion indicates maturation of proliferative cells (formed between day five-seven postlesion) into DpN. The present findings warrant future investigation of critical factors that govern the distinctive phases of DpN regeneration.

Item Type: Article
Funders: Ministry of Higher Education, Malaysia under the Fundamental Research Grant Scheme [600-IRMI/FRGS 5/3 (033/2019)]
Uncontrolled Keywords: Dopaminergic neuron; Neuroregeneration; Proliferation; Migration; Differentiation
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions: Faculty of Medicine > Medicine Department
Depositing User: Ms Koh Ai Peng
Date Deposited: 25 Jul 2024 06:59
Last Modified: 25 Jul 2024 06:59
URI: http://eprints.um.edu.my/id/eprint/46234

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