title: Upregulated expression of Nogo-A and NgR in an experimental model of focal microgyria regulates the migration, proliferation and self-renewal of subventricular zone neural progenitors.
abstract: Nogo-A and its receptor (NgR) were first described as myelin-associated inhibitors of neuronal regeneration in response to injury. In recent years, knowledge about the important role of the Nogo-A protein in several neuronal pathologies has grown considerably. Here, we employed a neonatal cortex freeze-lesion (NFL) model in neonatal rats and measured the expression of Nogo-A and NgR in the resulting cerebrocortical microdysgenesis 5-75 days after freezing injury. We observed marked upregulation of Nogo-A and NgR in protein levels. Furthermore, the migration of neural precursor cells (NPCs) derived from the subventricular zone (SVZ) toward the sits of injury was perturbed by treatment of NgR antagonist peptide NEP1-40. In vitro analysis showed that the knockdown of NgR by lentivirus-delivered siRNA promoted in axonal regeneration and SVZ-derived neural stem cell/progenitor cell (SVZ-NPCs) adhesion and migration, findings which were similar to the effects of NEP1-40. Taken together, our results indicate an important role for NgR in regulating the physiological processes of SVZ-NPCs. The observation of upregulated Nogo-A/NgR in lesion sites in the NFL model suggest that the effects of the perturbed Nogo-A are a key feature during the development and/or the progression of cortical malformation.
authors.affiliation: Department of Neurosurgery, General Hospital of the People's Liberation Army Chengdu Military Region, Chengdu, Sichuan, 610083, China.
authors.forename: Sixun
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Neurosurgery, General Hospital of the People's Liberation Army Chengdu Military Region, Chengdu, Sichuan, 610083, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Shu
authors.affiliation: Department of Neurosurgery, General Hospital of the People's Liberation Army Chengdu Military Region, Chengdu, Sichuan, 610083, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, General Hospital of the People's Liberation Army Chengdu Military Region, Chengdu, Sichuan, 610083, China.
authors.forename: Haidong
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Neurosurgery, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
authors.forename: Song
authors.initials: S
authors.lastname: Li
authors.affiliation: Central Laboratory, Teaching Hospital of Chengdu University of Traditional Chinese Medicine, 610075, China.
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery, General Hospital of the People's Liberation Army Chengdu Military Region, Chengdu, Sichuan, 610083, China. Electronic address: kuangyongqin@163.com.
authors.forename: Yongqin
authors.initials: Y
authors.lastname: Kuang
mesh_terms: D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D002540:Cerebral Cortex / Q000002:abnormalities / Q000293:injuries* / Q000473:pathology; D005260:Female; D005615:Freezing; D058851:GPI-Linked Proteins / Q000032:analysis / Q000378:metabolism; D020547:Lateral Ventricles / Q000378:metabolism / Q000473:pathology*; D009185:Myelin Proteins / Q000032:analysis / Q000378:metabolism*; D058953:Neural Stem Cells / Q000378:metabolism / Q000473:pathology*; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000032:analysis / Q000378:metabolism*
chemical_list: D058851:GPI-Linked Proteins; D009185:Myelin Proteins; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface; C000603197:Rtn4 protein, rat; C486581:Rtn4r protein, rat
keywords: Focal cortical dysplasia; Neonatal cortex freeze-lesion; Neural precursor cells; Nogo receptor; Nogo-A; Subventricular zone