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

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1387-1396
Number of pages10
JournalNeuropsychopharmacology
Volume37
Issue number6
DOIs
Publication statusPublished - 05-2012

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health

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