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Intrahippocampal Amyloid-β (1-40) Injections Injure Medial Septal Neurons in Rats

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Alzheimer's disease (AD) is a devastating disorder that leads to memory loss and dementia. Neurodegeneration of cholinergic neurons in the septum and other basal forebrain areas is evident in early stages of AD. Glutamatergic neurons are also affected early in AD. In these stages, amyloid-β-peptide (Aβ) plaques are present in the hippocampus and other cortices but not in the basal forebrain, which includes the septum. We postulate that early deposition of hippocampal Aβ damages the axon terminals of cholinergic and glutamatergic septo-hippocampal neurons, leading to their degeneration. To determine the mechanisms underlying septal degeneration, fibrillar Aβ1-40 was injected into the Cornu Ammonis (CA1) hippocampal region of rats. Controls were injected with reverse peptide Aβ40-1. A 16% reduction in NeuN+ cells was observed around the injection sites when compared to controls (p<0.05) one week after injections. Stereology was used to estimate the number of choline acetyl transferase (ChAT), glutamate and glutamic acid decarboxylase 67 (GAD67) immunoreactive septal neurons. Medial septal ChAT and glutamate immunoreactive neurons were reduced 38% and 26%, respectively by hippocampal injections of Aβ1-40 peptide in relation to controls. In contrast, the number of GAD67 inmunoreactive neurons was not significantly reduced. Apoptotic cells were detected in the medial septal region of Aβ1-40 treated animals but not in controls. These results indicate that limited Aβ-induced hippocampal lesions lead to an overall damage of vulnerable septal neuronal populations, most likely by Aβ interaction with septo-hippocampal axon terminals. Thus, axon terminals constitute an important target for novel therapeutics dedicated to control Aβ-induced toxicity.

Keywords: Alzheimer's disease; ChAT-immunoreactive neurons; GABAergic; cholinergic; fibrils; glutamatergic; hippocampu; intrahippocampal injections; medial septum; neurons

Document Type: Research Article


Publication date: 2011-12-01

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  • Current Alzheimer Research publishes peer-reviewed frontier review and research articles on all areas of Alzheimer's disease. This multidisciplinary journal will help in understanding the neurobiology, genetics, pathogenesis, and treatment strategies of Alzheimer's disease. The journal publishes objective reviews written by experts and leaders actively engaged in research using cellular, molecular, and animal models. The journal also covers original articles on recent research in fast emerging areas of molecular diagnostics, brain imaging, drug development and discovery, and clinical aspects of Alzheimer's disease. Manuscripts are encouraged that relate to the synergistic mechanism of Alzheimer's disease with other dementia and neurodegenerative disorders. Book reviews, meeting reports and letters-to-the-editor are also published. The journal is essential reading for researchers, educators and physicians with interest in age-related dementia and Alzheimer's disease. Current Alzheimer Research provides a comprehensive 'bird's-eye view' of the current state of Alzheimer's research for neuroscientists, clinicians, health science planners, granting, caregivers and families of this devastating disease.
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