title: Neuroglial alterations in rats submitted to the okadaic acid-induced model of dementia.
abstract: Several types of animal models have been developed to investigate Alzheimer's disease (AD). Okadaic acid (OA), a potent inhibitor of phosphatases 1 and 2A, induces characteristics that resemble AD-like pathology. Memory impairment induced by intra-hippocampal injection of OA has been reported, accompanied by remarkable neuropathological changes including hippocampal neurodegeneration, a paired helical filament-like phosphorylation of tau protein, and formation of β-amyloid containing plaque-like structures. Rats were submitted to bilateral intrahippocampal okadaic acid-injection (100 ng) and, 12 days after the surgery, behavioral and biochemical tests were performed. Using this model, we evaluated spatial cognitive deficit and neuroglial alterations, particularly astroglial protein markers such as glial fibrillary acidic protein (GFAP) and S100B, metabolism of glutamate, oxidative parameters and alterations in MAPKs. Our results indicate significant hippocampal changes, including increased GFAP, protein oxidation, and phosphorylation of p38(MAPK); and decreases in glutathione content, transporter EAAT2/GLT-1, and glutamine synthetase activity as well as a decrease in cerebrospinal fluid S100B. No alterations were observed in glutamate uptake activity and S100B content. In conclusion, the OA-induced model of dementia caused spatial cognitive deficit and oxidative stress in this model and, for the first time to our knowledge, specific astroglial alterations. Findings contribute to understanding diseases accompanied by cognitive deficits and the neural damage induced by AO administration.
authors: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul 90.035-003, Porto Alegre, RS, Brazil. anapaula.ufsc@gmail.com
authors: Ana Paula
authors: AP
authors: Costa
authors: Ana Carolina
authors: AC
authors: Tramontina
authors: Regina
authors: R
authors: Biasibetti
authors: Cristiane
authors: C
authors: Batassini
authors: Mark William
authors: MW
authors: Lopes
authors: Krista Minéia
authors: KM
authors: Wartchow
authors: Caren
authors: C
authors: Bernardi
authors: Lucas Silva
authors: LS
authors: Tortorelli
authors: Rodrigo Bainy
authors: RB
authors: Leal
authors: Carlos-Alberto
authors: CA
authors: Gonçalves
mesh_terms: D000818:Animals; D003072:Cognition Disorders / Q000134:cerebrospinal fluid / Q000150:complications / Q000378:metabolism; D003704:Dementia / Q000134:cerebrospinal fluid / Q000139:chemically induced / Q000150:complications / Q000378:metabolism* / Q000523:psychology; D004195:Disease Models, Animal; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008297:Male; D008845:Microinjections; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009414:Nerve Growth Factors / Q000134:cerebrospinal fluid / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism*; D019319:Okadaic Acid / Q000008:administration & dosage; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000134:cerebrospinal fluid / Q000378:metabolism
chemical_list: D027342:Excitatory Amino Acid Transporter 2; D005904:Glial Fibrillary Acidic Protein; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; C579158:S100b protein, rat; D019319:Okadaic Acid; D018698:Glutamic Acid; D020928:Mitogen-Activated Protein Kinases; D005974:Glutamate-Ammonia Ligase; D005978:Glutathione