单双侧侧脑室注射链脲佐菌素后线粒体功能障碍和认知功能的下降

Title:Mitochondrial Deficits Accompany Cognitive Decline Following Single Bilateral Intracerebroventricular Streptozotocin

Volume: 12 Issue: 8

Author(s): Ramesh K. Paidi, Dominic N Nthenge-Ngumbau, Raghavendra Singh, Thulasi Kankanala, Hina Mehta and Kochupurackal P. Mohanakumar

Affiliation:

关键词: 淀粉样变性，认知功能丧失，发动相关蛋白1，线粒体呼吸下降，非转基因动物模型，散发性阿尔茨海默病模型。

摘要: Background: Bilateral intracerebroventricular (ICV) administration of streptozotocin (STZ) causes Alzheimer’s disease (AD)-type neurodegeneration in rats. The model is increasingly used for investigating pathology and therapeutic strategies for AD. Objective: The present study investigated cognitive abilities in rats infused with STZ-ICV in relation to hippocampal and cortical mitochondrial functions during a period of 60 days. Methods: Cognitive functions were assayed in rats employing various mazes. Mitochondrial state-3-respiration, complex-I activity and dynamin related protein-1 (DRP-1) expression were measured respectively by oxygraph, spectrophotometry and immunoblot assay. Amyloidosis was investigated employing Congo red staining. Results: One-time ICV-STZ infused animals exhibited body-weight loss and impaired cognitive ability from 14^th day post-infusion. A significant loss of mitochondrial electron transport chain complex-I activity in the hippocampi and cortices was found by 14 days, and persisted up to 60 days following ICV-STZ infusion. Mitochondrial state-3 respiration was unaltered in these brain regions by 14 days, but significantly decreased from 21 days after STZ administration. DRP-1 expression was significantly increased in the hippocampi and cortices of these animals 21 days after infusion, but persisted only in the hippocampi up to 60 days. Congophilic granules indicative of amyloidosis were detected in the hippocampus by 21 days. Conclusion: Our results suggest that the non-genetic sporadic AD (sAD) rat model developed by single-time STZ-ICV infusion exhibits protein aggregation and dementia probably resulting from increased mitochondrial fragmentation and functional aberrations. The present study reinforces the validity of this model for studying pathogenesis and potential therapies of sAD.

Cite this article as:

Paidi K. Ramesh, Nthenge-Ngumbau N Dominic, Singh Raghavendra, Kankanala Thulasi, Mehta Hina and Mohanakumar P. Kochupurackal, Mitochondrial Deficits Accompany Cognitive Decline Following Single Bilateral Intracerebroventricular Streptozotocin, Current Alzheimer Research 2015; 12 (8) . https://dx.doi.org/10.2174/1567205012666150710112618