title: Ablation of neurogenesis attenuates recovery of motor function after focal cerebral ischemia in middle-aged mice.
abstract: Depletion of neurogenesis worsens functional outcome in young-adult mice after focal cerebral ischemia, but whether a similar effect occurs in older mice is unknown. Using middle-aged (12-month-old) transgenic (DCX-TK((+))) mice that express herpes simplex virus thymidine kinase (HSV-TK) under control of the doublecortin (DCX) promoter, we conditionally depleted DCX-positive cells in the subventricular zone (SVZ) and hippocampus by treatment with ganciclovir (GCV) for 14 days. Focal cerebral ischemia was induced by permanent occlusion of the middle cerebral artery (MCAO) or occlusion of the distal segment of middle cerebral artery (dMCAO) on day 14 of vehicle or GCV treatment and mice were killed 24 hr or 12 weeks later. Increased infarct volume or brain atrophy was found in GCV- compared to vehicle-treated middle-aged DCX-TK((+)) mice, both 24 hr after MCAO and 12 weeks after dMCAO. More severe motor deficits were also observed in GCV-treated, middle-aged DCX-TK((+)) transgenic mice at both time points. Our results indicate that ischemia-induced newborn neurons contribute to anatomical and functional outcome after experimental stroke in middle-aged mice.
authors.affiliation: Department of Pharmacology & Neuroscience, Institute for Aging and Alzheimer's Disease Research, University of North Texas, Fort Worth, Texas, United States of America.
authors.forename: Fen
authors.initials: F
authors.lastname: Sun
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Wang
authors.forename: Xiaoou
authors.initials: X
authors.lastname: Mao
authors.forename: Lin
authors.initials: L
authors.lastname: Xie
authors.forename: Kunlin
authors.initials: K
authors.lastname: Jin
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology*; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D015774:Ganciclovir / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000235:genetics; D055495:Neurogenesis / Q000187:drug effects*; D009479:Neuropeptides / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism
chemical_list: C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D013937:Thymidine Kinase; D015774:Ganciclovir