Neuroprotective effects of Neurotrophin-3 in MPTP-induced zebrafish Parkinson’s disease model

Introduction: Neurotrophin-3 (NT3) is a neuroprotective growth factor that induces the development, maintenance and survival of neurons. This study aims to localize NT3-expressing cells in the adult zebrafish brain and examine the role of NT3 in a zebrafish Parkinson’s disease (PD) model.Methods: Ce...

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Main Authors: Noor Azzizah Omar, Jaya Kumar, Seong Lin Teoh
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-11-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2023.1307447/full
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author Noor Azzizah Omar
Noor Azzizah Omar
Jaya Kumar
Seong Lin Teoh
author_facet Noor Azzizah Omar
Noor Azzizah Omar
Jaya Kumar
Seong Lin Teoh
author_sort Noor Azzizah Omar
collection DOAJ
description Introduction: Neurotrophin-3 (NT3) is a neuroprotective growth factor that induces the development, maintenance and survival of neurons. This study aims to localize NT3-expressing cells in the adult zebrafish brain and examine the role of NT3 in a zebrafish Parkinson’s disease (PD) model.Methods: Cellular localization of NT3 in adult zebrafish brains was conducted using in situ hybridization. Subsequently, adult zebrafish were injected intraperitoneally with 100 μg/g of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and treated with 400 ng/g body weight of recombinant NT3 (rNT3) via intracranial injection 24 h following MPTP injection. The fish were assessed for neurobehavioral, gene expression, immunohistology, and protein analysis on days 3, 5 and 10 post-MPTP injection.Results: Our findings showed that NT3 was extensively expressed throughout the adult zebrafish brain in neurons. Administration of rNT3 has significantly improved locomotor activity, with upregulation of th1, dat, ntf3 and bdnf gene expressions compared to MPTP-induced zebrafish. Dopaminergic neurons were also significantly increased in the zebrafish brain following rNT3 treatment. ELISA analysis reported raised GST and decreased caspase-3 levels on day 3 of assessment. The trophic changes of rNT3, however, decline as the assessment day progresses.Conclusion: This study is the first to examine the role of NT3 in the adult zebrafish PD model. NT3 has remarkable trophic effects in the zebrafish PD model. However, further study is needed to examine the dosage requirements and long-term effects of NT3 in PD.
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spelling doaj.art-0edfdc6891364135af46fbb6e8fedf782023-11-28T07:50:44ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-11-011410.3389/fphar.2023.13074471307447Neuroprotective effects of Neurotrophin-3 in MPTP-induced zebrafish Parkinson’s disease modelNoor Azzizah Omar0Noor Azzizah Omar1Jaya Kumar2Seong Lin Teoh3Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, MalaysiaDepartment of Medical Sciences, Faculty of Medicine and Health Sciences, Universiti Sains Islam Malaysia, Bandar Baru Nilai, MalaysiaDepartment of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, MalaysiaDepartment of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, MalaysiaIntroduction: Neurotrophin-3 (NT3) is a neuroprotective growth factor that induces the development, maintenance and survival of neurons. This study aims to localize NT3-expressing cells in the adult zebrafish brain and examine the role of NT3 in a zebrafish Parkinson’s disease (PD) model.Methods: Cellular localization of NT3 in adult zebrafish brains was conducted using in situ hybridization. Subsequently, adult zebrafish were injected intraperitoneally with 100 μg/g of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and treated with 400 ng/g body weight of recombinant NT3 (rNT3) via intracranial injection 24 h following MPTP injection. The fish were assessed for neurobehavioral, gene expression, immunohistology, and protein analysis on days 3, 5 and 10 post-MPTP injection.Results: Our findings showed that NT3 was extensively expressed throughout the adult zebrafish brain in neurons. Administration of rNT3 has significantly improved locomotor activity, with upregulation of th1, dat, ntf3 and bdnf gene expressions compared to MPTP-induced zebrafish. Dopaminergic neurons were also significantly increased in the zebrafish brain following rNT3 treatment. ELISA analysis reported raised GST and decreased caspase-3 levels on day 3 of assessment. The trophic changes of rNT3, however, decline as the assessment day progresses.Conclusion: This study is the first to examine the role of NT3 in the adult zebrafish PD model. NT3 has remarkable trophic effects in the zebrafish PD model. However, further study is needed to examine the dosage requirements and long-term effects of NT3 in PD.https://www.frontiersin.org/articles/10.3389/fphar.2023.1307447/fullneurodegenerative diseaseneurotrophin-3danio rerioneuronal survivalneurotoxindopaminergic neuron
spellingShingle Noor Azzizah Omar
Noor Azzizah Omar
Jaya Kumar
Seong Lin Teoh
Neuroprotective effects of Neurotrophin-3 in MPTP-induced zebrafish Parkinson’s disease model
Frontiers in Pharmacology
neurodegenerative disease
neurotrophin-3
danio rerio
neuronal survival
neurotoxin
dopaminergic neuron
title Neuroprotective effects of Neurotrophin-3 in MPTP-induced zebrafish Parkinson’s disease model
title_full Neuroprotective effects of Neurotrophin-3 in MPTP-induced zebrafish Parkinson’s disease model
title_fullStr Neuroprotective effects of Neurotrophin-3 in MPTP-induced zebrafish Parkinson’s disease model
title_full_unstemmed Neuroprotective effects of Neurotrophin-3 in MPTP-induced zebrafish Parkinson’s disease model
title_short Neuroprotective effects of Neurotrophin-3 in MPTP-induced zebrafish Parkinson’s disease model
title_sort neuroprotective effects of neurotrophin 3 in mptp induced zebrafish parkinson s disease model
topic neurodegenerative disease
neurotrophin-3
danio rerio
neuronal survival
neurotoxin
dopaminergic neuron
url https://www.frontiersin.org/articles/10.3389/fphar.2023.1307447/full
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