Laboratorio de Neurofarmacología, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla 72570, Mexico.
Pharmacol Biochem Behav. 2011 Mar;98(1):67-75. doi: 10.1016/j.pbb.2010.12.005. Epub 2010 Dec 14.
The Aβ(25-35) fraction mimics the toxic effects of the complete peptide Aβ(1-42) because this decapeptide is able to cause memory impairment and neurodegenerative events. Recent evidence has shown that the injection of Aβ(25-35) into the temporal cortex (TCx) of the rat increases the nitric oxide (NO) pathways with several consequences, such as neuronal loss in rats. Our aim was to investigate the effects of each NOS isoform by the prior injection of NOS inhibitors before the injection of the Aβ(25-35). One month after the treatment, the animals were tested for their spatial memory in the radial maze. The hippocampus (Hp) and TCx were assessed for NO production, nitration of proteins (3-NT), astrocytosis (GFAP), and neuronal loss. Our findings show a significant impairment in the memory caused by Aβ25-35 injection. In contrast NOS inhibitors plus Aβ25-35 cause a protection yielding a high performance in the memory test and reduction of cell damage in the TCx and the Hp. Particularly, iNOS is the major source of NO and related to the inflammatory response leading to the memory deficits. The inhibition of iNOS is an important target for neuronal protection against the toxicity of the Aβ25-35 over the long term.
β淀粉样肽（25-35）片段模拟完整肽β淀粉样肽（1-42）的毒性作用，因为这十肽能够导致记忆损伤和神经退行性病变。最近的证据表明，将β淀粉样肽（25-35）注射到大鼠的颞叶皮质（TCx）中会增加一氧化氮（NO）途径，导致多种后果，如大鼠神经元丢失。我们的目的是通过在注射β淀粉样肽（25-35）之前预先注射 NOS 抑制剂来研究每种 NOS 同工酶的作用。治疗一个月后，动物在放射状迷宫中接受空间记忆测试。评估海马（Hp）和 TCx 中的 NO 产生、蛋白质硝化（3-NT）、星形胶质细胞增生（GFAP）和神经元丢失。我们的发现表明，β淀粉样肽（25-35）注射引起的记忆损伤明显。相比之下，NOS 抑制剂加β淀粉样肽（25-35）会产生保护作用，使记忆测试中的表现提高，并减少 TCx 和 Hp 中的细胞损伤。特别是，iNOS 是 NO 的主要来源，与导致记忆缺陷的炎症反应有关。抑制 iNOS 是防止β淀粉样肽（25-35）长期毒性对神经元造成损伤的重要靶点。
