Limón I Daniel, Díaz Alfonso, Mendieta Liliana, Chamorro Germán, Espinosa Blanca, Zenteno Edgar, Guevara Jorge
Laboratorio de Neurofarmacología, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla, Mexico.
Neurosci Res. 2009 Feb;63(2):129-37. doi: 10.1016/j.neures.2008.11.006. Epub 2008 Nov 25.
beta-Amyloid plays an important role in the neurodegeneration process of Alzheimer's disease (AD), but its neurotoxic mechanisms are not clear. It has been associated with the increase of oxidative stress and cognitive impairment because the beta-amyloid peptide 25-35 (Abeta((25-35))) has the critical neurotoxic properties of the full-length Abeta(1-42). Our present study shows the role of Abeta((25-35)) when injected into the temporal cortex on the nitric oxide pathways, 3-nitrotyrosine, neuronal death, and the spatial memory of rats 1 month after the injection. Our data showed that Abeta((25-35)) increases oxidative stress, causes neuronal damage, and decreases spatial memory in rats. Notably, the injection of the fraction Abeta((25-35)) caused an increase of nNOS and iNOS immunoreactivity in the temporal cortex and hippocampus. We demonstrated a significant increase of reactive astrocytosis, which was accompanied by neuronal damage in the temporal cortex and hippocampus of rats injected with Abeta((25-35)). These data suggest that the fraction Abeta((25-35)) injected into the temporal cortex might contribute to understanding the role of nitric oxide on the biological changes related to the neuropathological progression and the memory impairment in AD.
β-淀粉样蛋白在阿尔茨海默病（AD）的神经退行性变过程中起重要作用，但其神经毒性机制尚不清楚。它与氧化应激增加和认知障碍有关，因为β-淀粉样肽25-35（Aβ（（25-35）））具有全长Aβ（1-42）的关键神经毒性特性。我们目前的研究显示了注射到颞叶皮质的Aβ（（25-35））在注射后1个月对大鼠一氧化氮途径、3-硝基酪氨酸、神经元死亡和空间记忆的作用。我们的数据显示，Aβ（（25-35））增加氧化应激，导致神经元损伤，并降低大鼠的空间记忆。值得注意的是，注射Aβ（（25-35））片段导致颞叶皮质和海马中nNOS和iNOS免疫反应性增加。我们证明了反应性星形胶质细胞增生显著增加，这伴随着注射Aβ（（25-35））的大鼠颞叶皮质和海马中的神经元损伤。这些数据表明，注射到颞叶皮质的Aβ（（25-35））片段可能有助于理解一氧化氮在与AD神经病理进展和记忆障碍相关的生物学变化中的作用。
