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Title: Leptin reverses corticosterone-induced inhibition of neural stem cell proliferation through activating the NR2B subunits of NMDA receptors

Highlights: • Leptin promotes the proliferation of neural stem cells isolated from embryonic mouse hippocampus. • Leptin reverses corticosterone-induced inhibition of neural stem cell proliferation. • The effects of leptin are partially mediated by upregulating NR2B subunits. - Abstract: Corticosterone inhibits the proliferation of hippocampal neural stem cells (NSCs). The removal of corticosterone-induced inhibition of NSCs proliferation has been reported to contribute to neural regeneration. Leptin has been shown to regulate brain development, improve angiogenesis, and promote neural regeneration; however, its effects on corticosterone-induced inhibition of NSCs proliferation remain unclear. Here we reported that leptin significantly promoted the proliferation of hippocampal NSCs in a concentration-dependent pattern. Also, leptin efficiently reversed the inhibition of NSCs proliferation induced by corticosterone. Interestingly, pre-treatment with non-specific NMDA antagonist MK-801, specific NR2B antagonist Ro 25-6981, or small interfering RNA (siRNA) targeting NR2B, significantly blocked the effect of leptin on corticosterone-induced inhibition of NSCs proliferation. Furthermore, corticosterone significantly reduced the protein expression of NR2B, whereas pre-treatment with leptin greatly reversed the attenuation of NR2B expression caused by corticosterone in cultured hippocampal NSCs. Our findings demonstrate that leptin reverses the corticosterone-induced inhibition of NSCs proliferation. This process is, at least partially mediated by increased expression of NR2Bmore » subunits of NMDA receptors.« less
Authors:
 [1] ;  [2] ;  [3] ;  [4] ;  [5] ;  [5] ;  [6] ;  [3] ;  [7]
  1. Anesthesia and Operation Center, Hainan Branch of Chinese PLA General Hospital, Hainan 572013 (China)
  2. (China)
  3. Department of Anesthesiology, PLA No. 306 Hospital, Beijing 100101 (China)
  4. Department of Anesthesiology, Beijing Military General Hospital of Chinese People’s Liberation Army, Beijing 100700 (China)
  5. Department of Head and Neck Surgery of Otolaryngology, PLA No. 306 Hospital, Beijing 100101 (China)
  6. Department of Anesthesiology, Armed Police General Hospital, Beijing 100039 (China)
  7. Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853 (China)
Publication Date:
OSTI Identifier:
22416400
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 447; Journal Issue: 1; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANGIOGENESIS; CELL PROLIFERATION; CONCENTRATION RATIO; CORTICOSTERONE; HIPPOCAMPUS; INHIBITION; LEPTIN; MICE; NERVE CELLS; RECEPTORS; REGENERATION; RNA; STEM CELLS