Naeem Abdul, Waseem Arshi, Khan Mohsin Ali, Robertson Avril Ab, Raza Syed Shadab
Laboratory for Stem Cell & Restorative Neurology, Department of Biotechnology, Era's Lucknow Medical College and Hospital, Era University, Sarfarazganj, Lucknow, 226003, India.
Era's Lucknow Medical College and Hospital, Era University, Sarfarazganj, Lucknow, 226003, India.
Mol Neurobiol. 2025 May;62(5):6041-6058. doi: 10.1007/s12035-024-04662-y. Epub 2024 Dec 20.
Alzheimer's disease (AD) is currently the seventh leading cause of death worldwide. In this study, we explored the critical role of autophagy in AD pathology using a streptozotocin (STZ)-induced AD model in Wistar rats. The experimental groups included sham, STZ-induced AD, and STZ + MCC950-treated animals. Our findings revealed that administering two doses of STZ (3 mg/kg) intracerebroventricular at the interval of 48 h (on days 0 and 2), triggered autophagy, as evidenced by elevated levels of autophagy markers such as LC3II, ULK1, Beclin1, Ambra1, Cathepsin B, and a reduction in p62 levels. Behavioral assessments, including the water maze and novel object recognition tests, confirmed cognitive deficits and memory impairment, while the open-field test indicated increased anxiety in STZ-induced AD rats. In particular, treating the STZ-induced AD group with MCC950 (50 mg/kg) decreased the overexpression of autophagy-related proteins, which was consistent with better behavioral outcomes and lower anxiety. Overall, this study highlights new insights into AD pathophysiology and suggests potential therapeutic avenues.
阿尔茨海默病（AD）目前是全球第七大死因。在本研究中，我们使用链脲佐菌素（STZ）诱导的Wistar大鼠AD模型，探讨了自噬在AD病理中的关键作用。实验组包括假手术组、STZ诱导的AD组和STZ + MCC950处理组动物。我们的研究结果显示，在第0天和第2天间隔48小时脑室内注射两剂STZ（3 mg/kg）会引发自噬，这可通过自噬标志物如LC3II、ULK1、Beclin1、Ambra1、组织蛋白酶B水平升高以及p62水平降低得到证明。行为评估，包括水迷宫和新物体识别测试，证实了认知缺陷和记忆障碍，而旷场试验表明STZ诱导的AD大鼠焦虑增加。特别是，用MCC950（50 mg/kg）治疗STZ诱导的AD组可降低自噬相关蛋白的过度表达，这与更好的行为结果和更低的焦虑水平一致。总体而言，本研究突出了对AD病理生理学的新见解，并提出了潜在的治疗途径。
