title: Pathological and biochemical alterations of astrocytes in ovariectomized rats injected with D-galactose: a potential contribution to Alzheimer's disease processes.
abstract: Astrocytes are implicated in the pathological changes of Alzheimer's disease. Our previous studies have demonstrated that estrogen deprivation and oxidative stress act synergistically to accelerate the progress of Alzheimer's disease. Long-term D-galactose injection combined with ovariectomy may serve as a rodent model for Alzheimer's disease. To address the potential contribution of astroglia to the Alzheimer's disease pathogenesis, we investigated pathological and biochemical alterations of astrocytes under this animal model. Ovariectomized rats injected with D-galactose for 2 weeks showed extensive localization of glial fibrillary acidic protein immunoreactive astrocytes and slightly elevated glutathione levels in the hippocampus without significant impairments in the water maze test and deficits of the cholinergic analyses, compared to the saline-injected rats. Ovariectomized rats injected with D-galactose for 6 weeks, however, exhibited degeneration of astrocytes and decreased glutathione levels in the hippocampus, accompanied with severe dysfunction of behavioral test and deficiency of cholinergic terminals. Electron microscopy further confirmed the pathological changes of astrocytes, especially in the aggregated area of synapse and brain microvessels. Consistent with degeneration of perivascular astrocytic endfeet, analysis of the horseradish peroxidase demonstrated an impairment of the blood-brain barrier permeability. These findings indicate that biochemical and pathological alterations of astrocytes may partially contribute to exacerbating neuronal deficits in the course of Alzheimer's disease. Restoring neuroprotective potential of astrocytes may be a useful therapeutic target for Alzheimer's disease and other neurodegenerative diseases.
authors.affiliation: Jiangsu Province Key Laboratory of Neurodegeneration, Department of Anatomy, Histology and Pharmacology of Nanjing Medical University, Nanjing, China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Hua
authors.forename: Ming
authors.initials: M
authors.lastname: Lei
authors.forename: Jiong
authors.initials: J
authors.lastname: Ding
authors.forename: Qunying
authors.initials: Q
authors.lastname: Han
authors.forename: Gang
authors.initials: G
authors.lastname: Hu
authors.forename: Ming
authors.initials: M
authors.lastname: Xiao
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D005690:Galactose / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D018782:Maze Learning / Q000187:drug effects; D046529:Microscopy, Electron, Transmission; D010052:Ovariectomy / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D013997:Time Factors
chemical_list: D005904:Glial Fibrillary Acidic Protein; D000110:Acetylcholinesterase; D005978:Glutathione; D005690:Galactose