Neuroprotective Screening of Natural Phenolics in an MPTP-Induced Model of Parkinson’s Disease Using Zebrafish Larvae

Abstract

This study investigates the neuroprotective effects of Ascorbic Acid (AA), Vanillic Acid (VA), and Ferulic Acid (FA) in a zebrafish model of Parkinson's Disease (PD), induced by MPTP. The research focuses on dopaminergic neurons, assessing responses to these compounds in terms of gene expression, mitochondrial dynamics, cellular stress responses, and cardiac health. Using quantitative polymerase chain reaction (qPCR) and Immunohistochemistry (IHC), this study examines the influence of AA, VA, and FA on dopaminergic function and neuronal health. AA was found to enhance dopaminergic function, indicated by upregulation of the dopamine transporter (DAT) gene and an increase in eGFP+ dopaminergic cells, suggesting improved dopamine reuptake and potential neuroprotection. AA also positively affected mitochondrial dynamics and stress response pathways, countering MPTP-induced dysregulation. VA influenced dopaminergic pathways and showed a nuanced effect on mitochondrial dynamics, though its impact on cardiac abnormalities was limited. FA displayed significant neuroprotective effects through modulation of gene expression related to dopaminergic neurons and mitochondrial dynamics, with extended benefits to cardiac health. These findings suggest that AA, VA, and FA may serve as potential protective interventions for Parkinson's Disease, reflecting various beneficial effects at the molecular and cellular levels. However, the translation of these results to practical clinical applications requires further investigation. This study contributes to the understanding of neuroprotective strategies in neurodegenerative diseases, highlighting the need to consider interactions between physiological systems. The direct applicability of these results in clinical PD settings warrants extensive future research.