title: Aquaporin-4 deficiency exacerbates brain oxidative damage and memory deficits induced by long-term ovarian hormone deprivation and D-galactose injection.
abstract: Astrocyte dysfunction is implicated in pathogenesis of certain neurological disorders including Alzheimer's disease (AD). A growing body of evidence indicates that water channel aquaporin-4 (AQP4) is a potential molecular target for the regulation astrocyte function. Recently, we reported that AQP4 expression was increased in the hippocampus of an AD mouse model established by long-term ovarian hormone deprivation combined with D-galactose (D-gal) exposure. However, pathophysiological roles and mechanisms of AQP4 up-regulation remain unclear. To address this issue, age-matched female wild-type and AQP4 null mice underwent ovariectomy, followed by D-gal administration for 8 wk. AQP4 null mice showed more severe brain oxidative stress, spatial learning and memory deficits, and basal forebrain cholinergic impairment than the wild-type controls. Notably, AQP4 null hippocampus contained more prominent amyloid-β production and loss of synapse-related proteins. These results suggested that ovariectomy and D-gal injection induced oxidative damage results in compensatory increases of AQP4 expression, and deficiency of AQP4 exacerbates brain oxidative stress and memory deficits. Therefore, regulation of astrocyte function by AQP4 may attenuate oxidative damage, offering a promising therapeutic strategy for AD.
authors.affiliation: Jiangsu Province Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Jiangsu Province Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, China.
authors.forename: Yushan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Jiangsu Province Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Kong
authors.affiliation: Jiangsu Province Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Rehabilitation Sciences, University of Kentucky Center For Excellence in Rural Health, Hazard, KY, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Marshall
authors.affiliation: Jiangsu Province Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Xiao
authors.affiliation: Jiangsu Province Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, China.
authors.forename: Jiong
authors.initials: J
authors.lastname: Ding
authors.affiliation: Jiangsu Province Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, China.
authors.forename: Junying
authors.initials: J
authors.lastname: Gao
authors.affiliation: Jiangsu Province Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Hu
mesh_terms: D000544:Alzheimer Disease; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D051401:Aquaporin 4 / Q000172:deficiency* / Q000235:genetics; D001253:Astrocytes / Q000502:physiology; D066187:Basal Forebrain / Q000503:physiopathology; D001921:Brain / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D005690:Galactose / Q000633:toxicity*; D005911:Gliosis / Q000503:physiopathology; D042341:Gonadal Hormones / Q000172:deficiency*; D006624:Hippocampus / Q000503:physiopathology; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000503:physiopathology*; D018345:Mice, Knockout; D010052:Ovariectomy; D018384:Oxidative Stress / Q000502:physiology*
chemical_list: D016229:Amyloid beta-Peptides; C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D042341:Gonadal Hormones; D005690:Galactose