MPTP induces neurodegeneration by modulating dopaminergic activity in catfish brain

Abstract

Tyrosine hydroxylase (Th) is an allosteric rate-limiting enzyme in catecholamine (CA) biosynthesis. The CAs, dopamine (DA), norepinephrine (NE), and epinephrine are important neurotransmitters wherein DA contributes a key role in the central nervous system of vertebrates. The present study evaluated DA and Th’s significance in DA-ergic activity and neurodegeneration upon 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposure in catfish. Further, the expression of certain brain-and ovary-related genes measured through qPCR were downregulated upon MPTP treatment which is in accordance with the decreased levels of L-Dopa, DA, and NE levels estimated through HPLC-ECD. Additionally, TEM analysis depicted structural disarray of brain upon MPTP exposure and also decreased serum levels of testosterone, 11-ketotestosterone, and estradiol-17β. MPTP treatment, in vitro, using primary brain cell culture resulted in diminished cell viability and increased ROS levels leading to elevated apoptotic cells significantly. Consequently, the study highlights the MPTP-induced neurodegeneration of the Th and DA-ergic activity in corroboration with female brain-related genes downregulation, also gonadal function as evidenced by depleted sex steroids level and low expression of ovary-related genes.