Differential Alterations in the Expression of AMPA Receptor and Its Trafficking Proteins in the Hippocampus Are Associated with Recognition Memory Impairment in the Rotenone-Parkinson's Disease Mouse Model: Neuroprotective Role of Bacopa monnieri Extract CDRI 08.

ABSTRACT

Parkinson's disease (PD), an age-associated neurodegenerative motor disorder, is associated with dementia and cognitive decline. However, the precise molecular insight into PD-induced cognitive decline is not fully understood. Here, we have investigated the possible alterations in the expression of glutamate receptor and its trafficking/scaffolding/regulatory proteins underlying the memory formation and neuroprotective effects of a specialized Bacopa monnieri extract, CDRI-08 (BME) in the hippocampus of the rotenone-induced PD mouse model. Our Western blotting and qRT-PCR data reveal that the PD-induced recognition memory decline is associated with significant upregulation of the AMPA receptor subunit GluR1 and downregulation of GluR2 subunit genes in the hippocampus of rotenone-affected mice as compared to the vehicle control. Further, expressions of the trafficking proteins are significantly upregulated in the hippocampus of rotenone-affected mice compared to the vehicle control. Our results also reveal that the above alterations in the hippocampus are associated with similar expression patterns of total CREB, pCREB, and BDNF. BME (CDRI-08, 200 mg/kg BW) reverses the expression of AMPA receptor subunits, their trafficking proteins differentially, and the transcriptional modulatory proteins depending on whether the BME treatment was given before or after the rotenone treatment. Our data suggest that expression of the above genes is significantly reversed in the BME pre-treated mice subjected to rotenone treatment towards their levels in the control mice compared to its treatment after rotenone administration. Our results provide the possible molecular basis underlying the rotenone-induced recognition memory decline, conditions mimicking the PD symptoms in mouse model and neuroprotective action of bacoside A and bacoside B (58%)-enriched Bacopa monnieri extract (BME) in the hippocampus.