Bacopa monnieri extract (CDRI-08) recovers recognition memory impairment by upregulation of GluR2 AMPA receptor subunit expression and reduced methylation of its cognate promoter in the hippocampus of rotenone-induced Parkinson’s disease mouse model

Abstract

Parkinson's disease (PD), an age-dependent neurodegenerative movement disorder, is attributed to the lossof dopaminergic neurons in the striatal SNPc, abnormal α-Synuclein accumulation that leads to complex movement disorders, cognitive dysfunction, and dementia in later stage, however, its precise molecular underpinning is not well known. In the proposed study, we aim to explore the effects of PD on the expression of the synaptic plasticity associated with AMPA receptor subunit GluR2, its epigenetic regulation, and investigate the possible therapeutic role of a well-characterized extract of an ancient Indian medicinal plantBacopa monniericalled CDRI-08 on the PD and memory impairment in rotenone-PD mouse model as presently there is no successful treatment available for curing the PD-induced pathologies. Our immunoblotting and qPCR data showed a significant upregulation of the GluR2 expression in the hippocampus of rotenone-treated mice as compared to the vehicle control group. Our MeDIP-qPCR data revealed that the increased GluR2 expression was significantly correlated with a decline in its promoter CpG methylation in the hippocampus of rotenone-treated mice. CDRI-08 treatment to the rotenone-treated mice significantly lowered the PD pathologies, and GluR2 expression with a subsequent increase in the GluR2 promoter methylation towards the control values in the hippocampus. The current study suggests one of the precise molecular events underlying PD, its effects on memory impairment, and the neurotherapeutic potential of Bacopa monnieri extract, CDRI-08, which might be useful for the treatment of PD-induced movement and cognitive impairments.