Amyloid peptides modify the expression of antioxidant repair enzymes and a potassium channel in the septohippocampal system.
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Alzheimer's disease (AD) is a progressive, neurodegenerative brain disorder characterized by extracellular accumulations of amyloid (A) peptides, intracellular accumulation of abnormal proteins, and early loss of basal forebrain neurons. Recent studies have indicated that the conformation of A is crucial for neuronal toxicity, with intermediate misfolded forms such as oligomers being more toxic than the final fibrillar forms. Our previous work shows that A blocks the potassium (K(+)) currents IM and IA in septal neurons, increasing firing rates, diminishing rhythmicity and firing coherence. Evidence also suggests that oxidative stress (OS) plays a role in AD pathogenesis. Thus we wished to determine the effect of oligomeric and fibrillar forms of A on septohippocampal damage, oxidative damage, and dysfunction in AD. Oligomeric and fibrillar forms of A were injected into the CA1 region of the hippocampus in live rats. The rats were sacrificed 24 hours and 1 month after A or sham injection to additionally evaluate the temporal effects. The expression levels of the K(+) voltage-gated channel, KQT-like subfamily, member 2 (KCNQ) and the OS-related genes superoxide dismutase 1, 8-oxoguanine DNA glycosylase, and monamine oxidase A, were analyzed in the hippocampus, medial, and lateral septum. Our results show that both forms of A exhibit time-dependent differential modulation of OS and K(+) channel genes in the analyzed regions. Importantly, we demonstrate that A injected into the hippocampus triggered changes in gene expression in anatomical regions distant from the injection site. Thus the A effect was transmitted to anatomically separate sites, because of the functional coupling of the brain structures.
Durn-Gonzlez, J., Michi, E. D., Elorza, B., Perez-Crdova, M. G., Pacheco-Otalora, L. F., Touhami, A., ... Colom, L. V.
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Durán-González, Jorge||Michi, Edna D||Elorza, Brisa||Perez-Córdova, Miriam G||Pacheco-Otalora, Luis F||Touhami, Ahmed||Paulson, Pamela||Perry, George||Murray, Ian V||Colom, Luis V
