Regulation of NMDA receptor 1 in the brain of mice exposed to PBDE 209

Abstract

Early childhood is a critical phase for the continuous development and maturation of several biological systems including brain. The critical period for the brain development is called brain growth spurt period. Exposure to the toxic agents during this period causes alterations in neuro-developmental process that results into neuronal dysfunction including learning and memory impairments during young and adulthood. Learning and memory are mainly regulated by N-methyl-D-aspartate receptor (NMDAR) especially NMDAR1 (NR1) subunit, an obligatory subunit of NMDAR. The NR1 subunit is required for the assembly of functional NMDARs. NR1 is subjected to transcriptional and non-transcriptional regulation. Transcriptional regulation is performed by CRE2 and REST/NRSF, trans-regulatory factors, on binding with cognate cis-regulatory sites present in NR1 promoter. Normal bursts of glutamate neurotransmission result in efficient synaptic transmission, excitation transcription coupling, and expression of the molecular substrates of long-term plasticity, growth and survival. On the other hand, abnormally intense bursts of glutamate result in overactivation of NMDAR that leads in causing excess influx of Ca2+ resulting excitotoxicity. This condition may be fatal to neuronal signals and can cause neurodegeneration resulting into cognitive dysfunction, including learning and memory impairments.