Alzheimer's disease (AD) is a progressive neurodegenerative disorder with cardinal features of cognitive dysfunction in an individual. Recently, the blockade of mitochondrial calcium uniporter (MCU) exhibits neuroprotective activity in experimental animals. However, the therapeutic potential of MCU has not yet been established in the management of AD. Therefore, the present study explored the therapeutic potential of either Ruthenium red (RR), a MCU blocker, or Spermine, a MCU opener, on the extent of mitochondrial calcium accumulation, function, integrity and bioenergetics in hippocampus, pre-frontal cortex and amygdale of ICV-STZ challenged rats. Experimental AD was induced in male rats by intracerebroventricular injection of streptozotocin (ICV-STZ) on day-1 (D-1) of the experimental protocol at a sub-diabetogenic dose (3 mg/kg) twice at an interval of 48 h into both rat lateral ventricles. RR attenuated ICV-STZ-induced memory-related behavioral abnormalities in Morris water maze and Y-maze tests. RR also attenuated ICV-STZ-induced decrease in the level of acetylcholine and activity of choline acetyltransferase and, increase in the activity of acetylcholinestarase in memory-sensitive rat brain regions. Further, RR attenuated mitochondrial toxicity in terms of reducing mitochondrial calcium accumulation and improving the mitochondrial function, integrity and bioenergetics in memory-sensitive brain regions of ICV-STZ challenged rats. Furthermore, RR attenuated the percentage of apoptotic cells in ICV-STZ challenged rat brain regions. However, Spermine did not alter ICV-STZ-induced behavioral, biochemical and molecular observations in any of the brain regions. These observations indicate the fact that the MCU blockage could be a potential therapeutic option in the management of sporadic type of AD.

阿尔茨海默病 (AD) 是一种进行性神经退行性疾病，具有个体认知功能障碍的主要特征。最近，线粒体钙单向转运蛋白 (MCU) 的阻断在实验动物中表现出神经保护活性。然而，MCU 在 AD 管理中的治疗潜力尚未确立。因此，本研究探讨了钌红 (RR)（一种 MCU 阻滞剂）或精胺（一种 MCU 开启剂）对海马、前额叶皮层和杏仁核中线粒体钙积累、功能、完整性和生物能量的程度的治疗潜力。 ICV-STZ 攻击的大鼠。通过在实验方案的第 1 天 (D-1) 以亚糖尿病剂量 (3 mg/kg) 以 48 小时间隔两次脑室内注射链脲佐菌素 (ICV-STZ) 在雄性大鼠中诱导实验性 AD两个大鼠侧脑室。在莫里斯水迷宫和 Y 迷宫测试中，RR 减弱了 ICV-STZ 诱导的记忆相关行为异常。RR 还减弱了 ICV-STZ 诱导的乙酰胆碱水平和胆碱乙酰转移酶活性的降低，以及记忆敏感大鼠大脑区域乙酰胆碱酯酶活性的增加。此外，在减少线粒体钙积累和改善 ICV-STZ 攻击大鼠的记忆敏感大脑区域的线粒体功能、完整性和生物能量学方面，RR 减弱了线粒体毒性。此外，RR 减弱了 ICV-STZ 攻击的大鼠大脑区域中凋亡细胞的百分比。然而，精胺并没有改变任何大脑区域中 ICV-STZ 诱导的行为、生化和分子观察。这些观察结果表明，MCU 阻塞可能是治疗散发型 AD 的潜在治疗选择。