title: Leptin reverses corticosterone-induced inhibition of neural stem cell proliferation through activating the NR2B subunits of NMDA receptors.
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 NR2B subunits of NMDA receptors.
authors.affiliation: Anesthesia and Operation Center, Hainan Branch of Chinese PLA General Hospital, Hainan 572013, China; Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Wen-Zhu
authors.initials: WZ
authors.lastname: Shi
authors.affiliation: Department of Anesthesiology, PLA No. 306 Hospital, Beijing 100101, China.
authors.forename: Yu-Liang
authors.initials: YL
authors.lastname: Miao
authors.affiliation: Department of Anesthesiology, Beijing Military General Hospital of Chinese People's Liberation Army, Beijing 100700, China.
authors.forename: Wen-Zhi
authors.initials: WZ
authors.lastname: Guo
authors.affiliation: Department of Head and Neck Surgery of Otolaryngology, PLA No. 306 Hospital, Beijing 100101, China. Electronic address: wwzwgk@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Head and Neck Surgery of Otolaryngology, PLA No. 306 Hospital, Beijing 100101, China.
authors.forename: Bao-Wei
authors.initials: BW
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Armed Police General Hospital, Beijing 100039, China.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: An
authors.affiliation: Department of Anesthesiology, PLA No. 306 Hospital, Beijing 100101, China.
authors.forename: Wei-Wu
authors.initials: WW
authors.lastname: Fang
authors.affiliation: Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853, China. Electronic address: elite2005gg@163.com.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Mi
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003345:Corticosterone / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism; D020738:Leptin / Q000494:pharmacology*; D051379:Mice; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology*; D010636:Phenols; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*
chemical_list: D020738:Leptin; D010636:Phenols; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; C109643:Ro 25-6981; D016291:Dizocilpine Maleate; D003345:Corticosterone
keywords: Corticosterone; Leptin; N-methyl-d-aspartate receptor; NR2B subunit; NSCs; Proliferation; siRNA