title: VEGF overexpression enhances the accumulation of phospho-S292 MeCP2 in reactive astrocytes in the adult rat striatum following cerebral ischemia.
abstract: OBJECTIVE
  Astrocytes can be reactivated after cerebral ischemia by expressing nestin and other characteristic markers of neural stem cells (NSCs). However, the epigenetic features of reactive astrocytes are not well known. Methyl-CpG-binding protein 2 (MeCP2) is a vital transcriptional modulator in brain development. Although the expression and function of some phosphorylated MeCP2 isoforms have been clarified, phospho-serine 292 (pS292) MeCP2 has not yet drawn much attention. In this study, we used western blot analysis and immunohistochemical and immunofluorescent staining to reveal the expressive features of pS292 MeCP2 and MeCP2 in the adult rat striatum following transient middle cerebral artery occlusion (MCAO).
  
  
  RESULTS
  We first discovered that the ischemia-induced expression of cytoplasmic pS292 MeCP2 is primarily accumulated in nestin-positive reactive astrocytes in the stroke-injured striatum. Moreover, the enhancement of astrocytic pS292 MeCP2 was correlated with the augmentation of VEGF in astrocytes, as determined by the substantial co-localization of pS292 MeCP2 and VEGF after stroke. Finally, the exogenous overproduction of VEGF further promoted the expression of pS292 MeCP2 in reactive astrocytes, and this effect was accompanied by a marked increase in reactive astrocytes. On the contrary, MeCP2 was predominantly expressed in the neuronal nucleus, and the level of this protein was not significantly altered after ischemic injury and VEGF overproduction.
  
  
  CONCLUSIONS
  Our data provide the first demonstration that overexpression of VEGF enhances the accumulation of pS292 MeCP2 in reactive astrocytes in the ischemic-injured rat striatum, implicating a pS292 MeCP2-related epigenetic role of exogenous VEGF in reactive astrocytes following cerebral ischemia.
authors.affiliation: Department of Neurobiology, Institute of Biomedical Sciences, State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, 131 Dong-An Road, Shanghai 200032, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Human Morphology, Institute of Medical Technology, Ningbo College of Health Sciences, 51 Xue-Fu Road, Ningbo 315100, Zhejiang, PR China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Ni
authors.affiliation: Department of Neurobiology, Institute of Biomedical Sciences, State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, 131 Dong-An Road, Shanghai 200032, PR China.
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Huang
authors.affiliation: Department of Neurobiology, Institute of Biomedical Sciences, State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, 131 Dong-An Road, Shanghai 200032, PR China.
authors.forename: Zeng-Wei
authors.initials: ZW
authors.lastname: Kou
authors.affiliation: Department of Neurobiology, Institute of Biomedical Sciences, State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, 131 Dong-An Road, Shanghai 200032, PR China. Electronic address: fysun@fudan.edu.cn.
authors.forename: Feng-Yan
authors.initials: FY
authors.lastname: Sun
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000378:metabolism*; D010766:Phosphorylation; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: C497394:Mecp2 protein, rat; D051783:Methyl-CpG-Binding Protein 2; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat
keywords: Cerebral ischemia; MeCP2 phosphorylation; Reactive astrocyte; Vascular endothelial growth factor (VEGF)