Identification of a Novel Rat NR2B Subunit Gene Promoter Region Variant and Its Association with Microwave-Induced Neuron Impairment

Abstract

Microwave radiation has been implicated in cognitive dysfunction and neuronal injury in animal models and in human investigations; however, the mechanism of these effects is unclear. In this study, single nucleotide polymorphism (SNP) sites in the rat GRIN2B promoter region were screened. The associations of these SNPs with microwave-induced rat brain dysfunction and with rat pheochromocytoma-12 (PC12) cell function were investigated. Wistar rats (n = 160) were exposed to microwave radiation (30 mW/cm2 for 5 min/day, 5 days/week, over a period of 2 months). Screening of the GRIN2B promoter region revealed a stable C-to-T variant at nucleotide position −217 that was not induced by microwave exposure. The learning and memory ability, amino acid contents in the hippocampus and cerebrospinal fluid, and NR2B expression were then investigated in the different genotypes. Following microwave exposure, NR2B protein expression decreased, while the Glu contents in the hippocampus and CSF increased, and memory impairment was observed in the TT genotype but not the CC and CT genotypes. In PC12 cells, the effects of the T allele were more pronounced than those of the C allele on transcription factor binding ability, transcriptional activity, NR2B mRNA, and protein expression. These effects may be related to the detrimental role of the T allele and the protective role of the C allele in rat brain function and PC12 cells exposed to microwave radiation.

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Acknowledgments

This work was supported by the National Basic Research Program of China (2011CB503706) and the National Natural Science Foundation of China (30970871). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Professor Gang-Qiao Zhou and Professor Ling-Qiang Zhang in Beijing Institute of Radiation Medicine for their kind help with SNP exploration.

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The authors declare no conflict of interest.

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Correspondence to Rui-Yun Peng or Xiang-Jun Hu.

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Li-Feng Wang and Da-Wei Tian are co-first authors.

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Wang, LF., Tian, DW., Li, HJ. et al. Identification of a Novel Rat NR2B Subunit Gene Promoter Region Variant and Its Association with Microwave-Induced Neuron Impairment. Mol Neurobiol 53, 2100–2111 (2016). https://doi.org/10.1007/s12035-015-9169-3

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Keywords

  • NR2B
  • Microwave
  • Promoter
  • Polymorphism
  • Neurons
  • Association