title: Central nervous system-specific knockout of Brg1 causes growth retardation and neuronal degeneration.
abstract: Changes in chromatin structure (chromatin remodeling) are essential regulatory processes for neuronal development, but the molecular mechanisms are unclear. The aim of the present study was to assess the effects of conditional knockout (Ko) of the Brahma-related gene-1 (Brg1) in the mouse central nervous system (CNS) on postnatal development. Brg1 was deleted in the CNS by crossing mice carrying the Brg1 conditional allele with a transgenic line expressing Cre under the control of the Nex 1 promoter. Brg1, PSD-95, NR2A and NR2B protein expressions were assessed using western blotting. Immunofluorescence, Nissl and TUNEL staining were used to assess cortical neuron viability. Hippocampal neurons were extracted from mouse embryos to observe the effects of neuronal degeneration associated with oxidative stress using Paraquat dichloride x-hydrate or 80% oxygen. Brg1(fx/fx);NEX-Cre mice were significantly smaller in both body size and brain size after P35 conditional Ko of Brg1 in mouse cortical progenitors. The amount of neurons and their dendritic branches were significantly reduced in Brg1 Ko cortexes during early postnatal development. Absence of Brg1 may result in increased number of astrocytes. Loss of Brg1 increased damaged and dying neurons associated with oxidative stress. Furthermore, loss of NR2A in the Brg1 Ko cortex during early postnatal development, and delayed the NR2B-NR2A switch. Therefore, Brg1 may play a critical role in neuronal growth by regulating the NR2B-NR2A switch. Our findings provide an insight in chromatin remodeling regulation in postnatal neuronal development.
authors.affiliation: West China Institute of Women and Children׳s Health, West China Second University Hospital, Sichuan University, China; Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, China; Third Affiliated Hospital of Nanchang University, Institute of Gastroenterology, No.20, Section 3, Renmin Nanlu, Chengdu 610041, Sichuan, China. Electronic address: dengli070@foxmail.com.
authors.forename: Li
authors.initials: L
authors.lastname: Deng
authors.affiliation: West China Institute of Women and Children׳s Health, West China Second University Hospital, Sichuan University, China; Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, China.
authors.forename: Guibo
authors.initials: G
authors.lastname: Li
authors.affiliation: Third Affiliated Hospital of Nanchang University, Institute of Gastroenterology, No.20, Section 3, Renmin Nanlu, Chengdu 610041, Sichuan, China.
authors.forename: Benqiang
authors.initials: B
authors.lastname: Rao
authors.affiliation: West China Institute of Women and Children׳s Health, West China Second University Hospital, Sichuan University, China; Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, China. Electronic address: huashunli2014@sina.com.
authors.forename: Huashun
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000473:pathology / Q000502:physiology; D004265:DNA Helicases / Q000172:deficiency* / Q000235:genetics; D018345:Mice, Knockout; D019579:Neocortex / Q000254:growth & development* / Q000473:pathology / Q000503:physiopathology*; D058953:Neural Stem Cells / Q000473:pathology / Q000502:physiology; D019636:Neurodegenerative Diseases / Q000473:pathology / Q000503:physiopathology*; D009687:Nuclear Proteins / Q000172:deficiency* / Q000235:genetics; D009929:Organ Size; D018384:Oxidative Stress / Q000502:physiology; D017966:Pyramidal Cells / Q000473:pathology / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics
chemical_list: C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D009687:Nuclear Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D014157:Transcription Factors; C513194:Smarca4 protein, mouse; D004265:DNA Helicases
keywords: Brg1; Chromatin remodeling; Degeneration; NR2B–NR2A switch; Neurons; Oxidative stress