Cerebrolysin restores MPTP-induced neuroinflammation, oxidative stress, and neurotransmitters in a Parkinson's disease zebrafish model

Abstract

Objective: To investigate the effect of cerebrolysin (CBL) on motor impairment, neuroinflammation, oxidative stress, and neurotransmitter profile in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson’s disease (PD) in zebrafish.

Methods: In the current study, zebrafish were treated with CBL at doses of 1.25, 2.5, and 5 mL/kg body weight for 7 consecutive days. MPTP (20 mg/kg body weight) was administered on alternative days-lst, 3rd, 5th, and 7th. On day 7, zebrafish were sacrificed, and their brains were isolated for biochemical, neurochemical, histopathological, IHC, and neurotransmitter analysis.

Results: The treatment with CBL significantly increased total distance traveled and the number of entries in the top zone, which was impaired by MPTP. CBL treatment significantly restored the level of glutathione, superoxide dismutase, and catalase while reducing malondialdehyde level. It also reduced the level of pro-inflammatory mediators interleukin-1β, interleukin-6, and tumor necrosis factor-α in the MPTP-induced PD in the zebrafish model. In histopathological evaluation, pyknotic cells and signs of inflammation were significantly reduced in CBL-treated groups. A significant dose-dependent reduction in glutamate, along with elevations in dopamine, gamma-aminobutyric acid, serotonin, and noradrenaline, was observed in zebrafish treated with CBL. An immunohistochemistry analysis demonstrated that Akt was phosphorylated promptly by CBL, which was downregulated in MPTP-induced PD in zebrafish.

Conclusions: These findings suggest that CBL exerts a neuroprotective effect through activation of Akt and may hold therapeutic potential for the treatment of this devastating neurological condition.

Keywords

Cerebrolysin / Neurodegeneration / Neuroinflammation / Oxidative stress / Zebrafish / Akt phosphorylation

Conflict of interest statement

The authors declare that there is no conflict of interest.

Funding

The research work is funded by ICMR, New Delhi (Grant No. 45/29/2022-PHA/BMS).

Data availability statement

The data supporting the findings of this study are available from the corresponding author upon request.

Authors’ contributions

DK designed the study and performed the experiments, statistical analysis, and writing of the manuscript. SS supervised and helped to draft the manuscript. All authors read and approved the final manuscript.

Publisher’s note

The Publisher of the Journal remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Acknowledgments

The chairman of ISF College of Pharmacy (An Autonomous College), Moga (Punjab), Mr. Parveen Garg, is gratefully acknowledged by the authors for his wonderful encouragement and support of this study. We are also grateful to Prof. (Dr.) Y.K. Gupta, President of AIIMS Bhopal and Jammu, and Chairman of the Reviewing Committee of ISF College of Pharmacy (An autonomous college), for his ongoing assistance and manuscript reviewing. The authors also acknowledge IK Gujaral, Punjab Technical University, Jalandhar, Punjab, India, for providing all the necessary support for the research.

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