Methyl CpG-binding protein 2 participating in the regulation of differentiation plasticity of nerve regeneration in the basal ganglia after ischemic stroke

Abstract

Background It is accepted that cerebral ischemia induces neurogenesis and neural stem cells (NSCs) differentiation in non-neurogenic regions (especially in the basal ganglia). However, the mechanisms possibly involved in modulating the differentiation plasticity of NSCs are still let to known. This study aims to investigate the possible epigenetic mechanisms involved in the differentiation process of NSCs after ischemic stroke. Methods Western blotting analysis was used to detect the protein levels of methyl CpG-binding protien 2 (MeCP2) and phosphorylated MeCP2 (pMeCP2) in the ischemic basal ganglia of rat model at 3 d following middle cerebral artery occlusion (MCAO). Immunohistochemical staining was performed to observe the cellular distribution of MeCP2 and pMeCP2, the cellular colocalization of pMeCP2 with NSCs marker nestin and neuronal marker microtubule-associated protein 2 (MAP-2) in the ischemic basal ganglia of rat brains. Results 1) MeCP2 was phosphorylated in the basal ganglia after ischemic stroke, forming pMeCP2. MeCP2 positive cell number was decreased in the ischemic basal ganglia (t = 12.239, P = 0.000), while pMeCP2 positive cell number was increased in the ischemic basal ganglia (t = 5.808, P = 0.000). 2) Ischemic stroke induced a reduction of MeCP2 levels in the nucleus (t = 14.949, P = 0.000) and an elevation of pMeCP2 levels in the cytoplasm (t = 5.026, P = 0.001). 3) MeCP2 phosphorylation mediated the translocation of MeCP2 from nucleus to cytoplasm. 4) pMeCP2 was colocalized with NSCs marker protein nestin in the ischemic basal ganglia at 3 d after MCAO; pMeCP2 was colocalized with the neuronal marker MAP-2 in the ischemic basal ganglia at 1 week after MCAO. Conclusion Ischemic stroke-induced MeCP2 phosphorylation was able to alter the spatial distribution of MeCP2, transferring it from nucleus to cytoplasm and affecting its biological functions. This study further improved our awareness of brain neurogenesis in adult animals, providing new perspective for making use of neuronal regeneration in the treatment of neurodegenerative diseases and nerve injuries.

doi：10.3969/j.issn.1672-6731.2013.11.009