Neuroglial alterations in rats submitted to the okadaic acid-induced model of dementia. Academic Article uri icon

Overview

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

  • Costa, Ana Paula
  • Tramontina, Ana Carolina
  • Biasibetti, Regina
  • Batassini, Cristiane
  • Lopes, Mark William
  • Wartchow, Krista Minéia
  • Bernardi, Caren
  • Tortorelli, Lucas Silva
  • Leal, Rodrigo Bainy
  • Gonçalves, Carlos-Alberto

publication date

  • October 1, 2011

Research

keywords

  • Dementia
  • Disease Models, Animal
  • Hippocampus
  • Neuroglia

Identity

Scopus Document Identifier

  • 81355127353

Digital Object Identifier (DOI)

  • 10.1016/j.bbr.2011.09.035

PubMed ID

  • 21982813

Additional Document Info

volume

  • 226

issue

  • 2