PUBLICATION
Manganese chloride (MnCl2) induced novel model of Parkinson's disease in adult Zebrafish; Involvement of oxidative stress, neuroinflammation and apoptosis pathway
- Authors
- Nadig, A.P.R., Huwaimel, B., Alobaida, A., Khafagy, E.S., Alotaibi, H.F., Moin, A., Lila, A.S.A., Suman, ., M, S., Krishna, K.L.
- ID
- ZDB-PUB-220923-18
- Date
- 2022
- Source
- Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 155: 113697 (Journal)
- Registered Authors
- Keywords
- Manganese Chloride, Non-motor symptoms, Parkinson's disease, Pro-inflammatory cytokines, Tyrosine hydroxylase, Zebrafish
- MeSH Terms
-
- 3,4-Dihydroxyphenylacetic Acid/metabolism
- Amino Acids/metabolism
- Animals
- Apoptosis
- Brain-Derived Neurotrophic Factor/metabolism
- Cytokines/metabolism
- Dopamine/metabolism
- Neuroinflammatory Diseases
- Oxidative Stress
- Parkinson Disease*/drug therapy
- Zebrafish*/metabolism
- PubMed
- 36137406 Full text @ Biomed. Pharmacother.
Citation
Nadig, A.P.R., Huwaimel, B., Alobaida, A., Khafagy, E.S., Alotaibi, H.F., Moin, A., Lila, A.S.A., Suman, ., M, S., Krishna, K.L. (2022) Manganese chloride (MnCl2) induced novel model of Parkinson's disease in adult Zebrafish; Involvement of oxidative stress, neuroinflammation and apoptosis pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 155:113697.
Abstract
Parkinson's disease (PD) is a progressive neurodegenerative disorder imposing a severe health and socioeconomic burden worldwide. Existing pharmacological approaches for developing PD are poorly developed and do not represent all the characteristics of disease pathology. Developing cost-effective, reliable Zebrafish (ZF) model will meet this gap. The present study was conceived to develop a reliable PD model in the ZF using manganese chloride (MnCl2). Here, we report that chronic exposure to 2 mM MnCl2 for 21 days produced non-motor and motor PD-like symptoms in adult ZF. Compared with control fish, MnCl2-treated fish showed reduced locomotory activity, indicating a deficit in motor function. In the light-dark box test, MnCl2-treated fish exhibited anxiety and depression-like behavior. MnCl2-treated fish exhibited a less olfactory preference for amino acids, indicating olfactory dysfunction. These behavioral symptoms were associated with decreased dopamine and increased DOPAC levels. Furthermore, oxidative stress-mediated apoptotic pathway, decreased brain derived neurotropic factor (BDNF) and increased pro-inflammatory cytokines levels were observed upon chronic exposure to MnCl2 in the brain of ZF. Thus, MnCl2-induced PD in ZF can be a cost-effective PD model in the drug discovery process. Moreover, this model could be potentially utilized to investigate the molecular pathways underlying the multifaceted pathophysiology which leads to PD using relatively inexpensive species. MnCl2 being heavy metal may have other side effects in addition to neurotoxicity. Our model recapitulates most of the hallmarks of PD, but not all pathological processes are involved. Future studies are required to recapitulate the complete pathophysiology of PD.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping