Neuropathologically, Alzheimer's disease (AD) is characterized by neuritic plaques and neurofibrillary tangles. Evidence has suggested that a protein called B-amyloid (BA) is a major component of the neuritic plaques and may playa role in the neurodegeneration seen in AD. The cellular mechanisms by which BA induces neurotoxicity, however, are still unclear. Recent evidence suggests that the aggregational state of BA may be relevant to its neurotoxicity. Whether portions of the BA protein or the entire sequence produces neurotoxicity in neurons, however, remains a controversy. Still another controversy is whether BA is directly neurotoxic to neurons or whether it increases the vulnerability of neurons. Recent evidence reported by Doman, Kang, McCampbell and Kang, that injections of BA(25-35) with a low dose of ibotenic acid into the hippocampus did disrupt the acquisition of spatial learning in the rat, supports the vulnerability hypothesis. They suggest that the synergistic effect between BA and ibotenic acid may have produced the neurotoxic effect. In light of recent evidence (McCampbell, Peterson and Tinkler, unpublished) that injections of BA(1-42) alone did not disrupt the retention of a spatial learning task, in this study we assessed the increased vulnerability hypothesis by co-injecting fiA(1-42) with a subthreshold dose of ibotenic acid into the hippocampus of male rats. Another problem related to fiA's neurotoxicity may concern the extent of hippocampal damage it produces. Therefore, we assessed the effects of multiple injections of fiA(1-42) and ibotenic acid into the hippocampus of male rats. Although preliminary, the results of this study conclude that coinjections of fiA(1-42) and ibotenic acid do not disrupt the retention of a spatial learning task.
Biology | Neuroscience and Neurobiology | Psychology
Pequette '94, Jason, "Toward an Understanding of Alzheimer's Disease: The Effects of B-Amyloid(1-42) and Ibotenic Acid on the Retention of a Spatial learning Task in Rats F:ollowing Multiple Injections into the Hippocampus" (1994). Honors Projects. 42.