title: Interaction of nNOS with PSD-95 negatively controls regenerative repair after stroke.
abstract: Stroke is a major public health concern. The lack of effective therapies heightens the need for new therapeutic targets. Mammalian brain has the ability to rewire itself to restore lost functionalities. Promoting regenerative repair, including neurogenesis and dendritic remodeling, may offer a new therapeutic strategy for the treatment of stroke. Here, we report that interaction of neuronal nitric oxide synthase (nNOS) with the protein postsynaptic density-95 (PSD-95) negatively controls regenerative repair after stroke in rats. Dissociating nNOS-PSD-95 coupling in neurons promotes neuronal differentiation of neural stem cells (NSCs), facilitates the migration of newborn cells into the injured area, and enhances neurite growth of newborn neurons and dendritic spine formation of mature neurons in the ischemic brain of rats. More importantly, blocking nNOS-PSD-95 binding during the recovery stage improves stroke outcome via the promotion of regenerative repair in rats. Histone deacetylase 2 in NSCs may mediate the role of nNOS-PSD-95 association. Thus, nNOS-PSD-95 can serve as a target for regenerative repair after stroke.
authors.affiliation: Laboratory of Cerebrovascular Disease, Institution of Stem Cells and Neuroregeneration, and Departments of Pharmacology and.
authors.forename: Chun-Xia
authors.initials: CX
authors.lastname: Luo
authors.affiliation: Laboratory of Cerebrovascular Disease, Departments of Pharmacology and.
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Lin
authors.affiliation: Laboratory of Cerebrovascular Disease, Departments of Pharmacology and.
authors.forename: Xiao-Dan
authors.initials: XD
authors.lastname: Qian
authors.affiliation: Laboratory of Cerebrovascular Disease, Departments of Pharmacology and.
authors.forename: Ying
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Laboratory of Cerebrovascular Disease, Departments of Pharmacology and.
authors.forename: Hai-Hui
authors.initials: HH
authors.lastname: Zhou
authors.affiliation: Laboratory of Cerebrovascular Disease, Departments of Pharmacology and.
authors.forename: Xing
authors.initials: X
authors.lastname: Jin
authors.affiliation: Laboratory of Cerebrovascular Disease, Departments of Pharmacology and.
authors.forename: Huan-Yu
authors.initials: HY
authors.lastname: Ni
authors.affiliation: Laboratory of Cerebrovascular Disease, Departments of Pharmacology and.
authors.forename: Feng-Yun
authors.initials: FY
authors.lastname: Zhang
authors.affiliation: Laboratory of Cerebrovascular Disease, Departments of Pharmacology and.
authors.forename: Cheng
authors.initials: C
authors.lastname: Qin
authors.affiliation: Medicinal Chemistry, School of Pharmacy, Nanjing Medical University, Nanjing 210029, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.affiliation: Laboratory of Cerebrovascular Disease, Departments of Pharmacology and.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institution of Stem Cells and Neuroregeneration, and Departments of Pharmacology and.
authors.forename: Hai-Yin
authors.initials: HY
authors.lastname: Wu
authors.affiliation: Laboratory of Cerebrovascular Disease, Departments of Pharmacology and.
authors.forename: Lei
authors.initials: L
authors.lastname: Chang
authors.affiliation: Laboratory of Cerebrovascular Disease, Institution of Stem Cells and Neuroregeneration, and Departments of Pharmacology and dyzhu@njmu.edu.cn.
authors.forename: Dong-Ya
authors.initials: DY
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology / Q000648:ultrastructure; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D018920:Coculture Techniques; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein; D004622:Embryo, Mammalian; D005947:Glucose / Q000172:deficiency; D056464:Histone Deacetylase 2 / Q000235:genetics / Q000378:metabolism; D000860:Hypoxia / Q000503:physiopathology; D020244:Infarction, Middle Cerebral Artery / Q000503:physiopathology / Q000601:surgery*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000502:physiology / Q000637:transplantation*; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000502:physiology*
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D052248:Nitric Oxide Synthase Type I; C533426:Hdac2 protein, rat; D056464:Histone Deacetylase 2; D005947:Glucose
keywords: HDAC2; PSD-95; nNOS; neurogenesis; stem cells; stroke