CDRI-08 Attenuates REST/NRSF-Mediated Expression of NMDAR1 Gene in PBDE-209-Exposed Mice Brain

CDRI-08 is a standardized bacoside enriched ethanolic extract of Bacopa monnieri, a nootropic plant. We reported that CDRI-08 attenuated oxidative stress and memory impairment in mice, induced by a flame retardant, PBDE-209. In order to explore the mechanism, present study was designed to examine the role of CDRI-08 on the expression of NMDAR1 (NR1) and the binding of REST/NRSF to NR1 promoter against postnatal exposure of PBDE-209. Male mice pups were orally supplemented with CDRI-08 at the doses of 40, 80, or 120 mg/kg along with PBDE-209 (20 mg/kg) during PND 3-10 and frontal cortex and hippocampus were collected at PND 11 and 60 to study the expression and regulation of NR1 by RT-PCR and electrophoretic mobility shift assay, respectively. The findings showed upregulated expression of NR1 and decreased binding of REST/NRSF to NR1 promoter after postnatal exposure of PBDE-209. Interestingly, supplementation with CDRI-08 significantly restored the expression of NR1 and binding of REST/NRSF to NR1 promoter near to the control value at the dose of 120 mg/kg. In conclusion, the results suggest that CDRI-08 possibly acts on glutamatergic system through expression and regulation of NR1 and may restore memory, impaired by PBDE-209 as reported in our previous study.