NMDA receptors promote neurogenesis in the neonatal rat subventricular zone following hypoxic‑ischemic injury

Lai,Qingwei; Hu,Peng; Li,Qingyun; Li,Xinyu; Yuan,Rui; Tang,Xiaohong; Wang,Wei; Li,Xiaoquan; Fan,Hongbin; Yin,Xiaoxing

doi:10.3892/mmr.2015.4501

NMDA receptors promote neurogenesis in the neonatal rat subventricular zone following hypoxic‑ischemic injury

Authors:
- Qingwei Lai
- Peng Hu
- Qingyun Li
- Xinyu Li
- Rui Yuan
- Xiaohong Tang
- Wei Wang
- Xiaoquan Li
- Hongbin Fan
- Xiaoxing Yin
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Affiliations: Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China, Department of Clinical Pharmacology, School of Pharmacy, Xuzhou Medical College, Xuzhou, Jiangsu 221004, P.R. China
Published online on: November 4, 2015 https://doi.org/10.3892/mmr.2015.4501
Pages: 206-212
Copyright: © Lai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Evidence suggests the involvement of N‑methyl‑D‑ aspartate receptors (NMDAR) in the regulation of neurogenesis. Functional properties of NMDAR are strongly influenced by the type of NR2 subunits in the receptor complex. NR2A‑ and NR2B‑containing receptors are expressed in neonatal forebrain regions, such as the subventricular zone (SVZ). The aim of the present study was to examine the effect of the protein expression of hypoxic‑ischemic injury NMDAR subunits 2A and 2B in the SVZ of neonatal rats. Expression of these and other proteins of interest was performed using immunohistochemistry. The results showed that NR2A expression was decreased at 6 h after hypoxic‑ischemic injury. By contrast, a significant increase in NR2B expression was observed at 24 h after hypoxic‑ischemic injury, induced by the clamping of the right common carotid artery. The functional effect of NMDAR subunits on neurogenesis was also examined by quantifying Nestin and doublecortin (DCX), the microtubule‑associated protein expressed only in immature neurons. In addition, the effects of selective non‑competitive NMDAR antagonist MK‑801 (0.5 mg/kg), NR2B antagonist Ro25‑6981 (5 mg/kg), and NR2A antagonist NVP‑AAM077 (5 mg/kg) administered 30 min prior to the hypoxic‑ischemic injury were examined. The number of Nestin‑ and DCX‑positive cells increased significantly 48 h after hypoxic‑ischemic injury, which was reverted by the MK‑801 and Ro25‑6981 antagonists. Notably, NVP‑AAM077 had no significant effect on the expression of Nestin and DCX. In conclusion, the results of the present study demonstrate that hypoxia‑ischemia inhibited the expression of NR2A, but promoted the expression of NR2B. Furthermore, NMDAR promoted neurogenesis in the SVZ of neonatal brains.

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