Prenatal NMDA receptor antagonism impaired proliferation of neuronal progenitor, leading to fewer glutamatergic neurons in the prefrontal cortex

Kazuya Toriumi, Akihiro Mouri, Shiho Narusawa, Yuki Aoyama, Natsumi Ikawa, Lingling Lu, Taku Nagai, Takayoshi Mamiya, Hyoung Chun Kim, Toshitaka Nabeshima

研究成果: Article査読

30 被引用数 (Scopus)

抄録

N-methyl-D-aspartate (NMDA) receptor is a glutamate receptor which has an important role on mammalian brain development. We have reported that prenatal treatment with phencyclidine (PCP), a NMDA receptor antagonist, induces long-lasting behavioral deficits and neurochemical changes. However, the mechanism by which the prenatal antagonism of NMDA receptor affects neurodevelopment, resulting in behavioral deficits, has remained unclear. Here, we report that prenatal NMDA receptor antagonism impaired the proliferation of neuronal progenitors, leading to a decrease in the progenitor pool in the ventricular and the subventricular zone. Furthermore, using a PCR array focused on neurogenesis and neuronal stem cells, we evaluated changes in gene expression causing the impairment of neuronal progenitor proliferation and found aberrant gene expression, such as Notch2 and Ntn1, in prenatal PCP-treated mice. Consequently, the density of glutamatergic neurons in the prefrontal cortex was decreased, probably resulting in glutamatergic hypofunction. Prenatal PCP-treated mice displayed behavioral deficits in cognitive memory and sensorimotor gating until adulthood. These findings suggest that NMDA receptors regulate the proliferation and maturation of progenitor cells for glutamatergic neuron during neurodevelopment, probably via the regulation of gene expression.

本文言語English
ページ(範囲)1387-1396
ページ数10
ジャーナルNeuropsychopharmacology
37
6
DOI
出版ステータスPublished - 05-2012
外部発表はい

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health

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