Abstract

Pathologically, Alzheimer's disease (AD) is characterized by deposits of neuritic plaques (NP) and neurofibrillary tangles (NFT) typically found in the cerebral cortex, hippocampus, and basal forebrain. Increasing evidence suggests that the major constituent of NP, a B-amyloid protein(BAP) composed of 39-42 amino acids, possesses neurotoxic properties. It has been reputed that the neurotoxic properties of BAP(1-40) may be dependent on the aggregational state of the peptide. Recent studies have demonstrated in vitro that a fragment of the B-amyloid protein, BAP(25-35), disrupts intracellular calcium homeostasis, decreases neuronal survival, and potentiates the toxicity of excitatory amino acids (EAA). While some evidence supports the direct in vivo toxicity of BAP, the extent of neuronal damage has not been compared with standard lesions made by EAAs. Moreover, currently the effects of intracerebral injections of BAP(2535) on learning and memory in the rat is unknown. Therefore, in this study a comparative behavioral and histological assessment was conducted following bilateral intrahippocampal injections of BAP(25-35), ibotenic acid (IBO), BAP(25-35)+IBO, and incubated BAP(25-35) (1 week at 37 C). A radial arm maze and Morris water maze were utilized for comparative learning and memory assessment. Preliminary results indicate that there is a clear disruption of learning performance in animals co-injected with low doses of BAP(25-35) (4nmol/ul) + IBO (lug/ul) while identical doses injected separately had no effect. The deficits in learning observed following injections of BAP(25-35)+IBO and the high does of IBO was not, however, due to disruptions in motor behavior as there was no difference found between groups on a treadmill test in those that ran the maze and those that did not. In support of the behavioral results, preliminary histological analyses revealed cytotoxic effects in the hippocampus following injections of BAP(25-35) '+ IBO or a high does of IBO. This study suggests that the injection of BAP (25-35) into the hippocampus promotes the vulnerability of neurons to excitotoxic damage in vivo and disrupts learning/memory in rats.

Disciplines

Psychology

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Psychology Commons

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