The present study evaluated the effects of s-nitrosoglutathione (GSNO), a nitrosothiol and sustained NO releaser, on experimental model of sporadic Alzheimer`s disease (sAD) in rats. Levels of Aβ40, Aβ42 and BDNF were assessed in brain hippocampal homogenates for correlative purposes. Intracerebroventricular-Streptozotocin (icv-STZ) induced increased escape latencies (acquisition) and reduced time in target quadrant (probe trial) in Morris Water Maze (MWM) test at 3 months post icv-STZ administration. These behavioural changes were associated with increased Aβ depositions and lowered BDNF levels in brain hippocampal homogenates. Pre-treatment with GSNO (50 μg/kg/day), reduced the icv-STZ induced cognitive deficits in acquisition and probe trials in the MWM. The icv-STZ induced elevations in Aβ40 and Aβ42 and reduced levels of BDNF in hippocampal homogenates were also attenuated after GSNO treatment in these rats. The NO-precursor, l-arginine (100 mg/kg) induced similar effects on behavioural and biochemical parameters tested but was marginally less consistent as compared to those seen with GSNO. The results suggest that GSNO ameliorates the cognitive deficits and associated brain biochemical changes in this experimental model of sporadic AD, and NO-BDNF interactions could play crucial role in these effects.

本研究评估了s-亚硝基谷胱甘肽（GSNO），亚硝基硫醇和持续的NO释放剂对大鼠偶发性阿尔茨海默病（sAD）实验模型的影响。为了相关目的，在脑海马匀浆中评估了Aβ40，Aβ42和BDNF的水平。在icv-STZ给药后3个月的莫里斯水迷宫（MWM）测试中，脑室内链脲佐菌素（icv-STZ）诱导了逃逸潜伏期的增加（获取）并缩短了目标象限的时间（探针试验）。这些行为改变与脑海马匀浆中Aβ沉积增加和BDNF水平降低有关。用GSNO（50μg/ kg /天）进行的预处理减少了icv-STZ在MWM中的获取和探查试验中引起的认知缺陷。GSNO处理后，icv-STZ诱导的大鼠海马匀浆中Aβ40和Aβ42的升高以及BDNF的水平降低也减弱了。没有先驱者1-精氨酸（100 mg / kg）对测试的行为和生化参数具有相似的作用，但与GSNO相比，一致性稍差。结果表明，GSNO改善了这种散发性AD实验模型中的认知缺陷和相关的脑生化变化，NO-BDNF相互作用可能在这些作用中起关键作用。