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Published on: January 22, 2017
Everolimus alleviates cognitive dysfunction in 5×FAD mice by regulating mitochondrial function and oxidative stress
Fei Li1, Yun Chen2, WenRong Zheng2
1Department of Pharmacy, Fuzhou University Affiliated Provincial Hospital, Fuzhou, 350001, China; School of Pharmacy, Fujian Medical University, Fuzhou, 350122, China.
Abstract:
Everolimus, a well-characterized inhibitor of the mammalian target of rapamycin (mTOR), has been extensively profiled in both preclinical and clinical studies. Accumulating evidence from recent studies suggests that mTOR inhibitors potentially possess the capacity to protect against various age-related diseases. Nevertheless, the impacts of Everolimus on cognitive function and the underlying mechanisms remain underexplored. In this study, we systematically evaluated the effects of varying doses of Everolimus (administered via intraperitoneal injection every other day for 8 weeks) on the cognitive ability of 5 × FAD mice. The learning and spatial memory of 5 × FAD mice were improved after Everolimus administration, with normal morphology and more pyramidal cells were detected in the hippocampi. Our findings suggest that Everolimus alleviates cognitive impairment in 5 × FAD mice through enhancing mitochondrial function, reducing oxidative stress, and improving energy metabolism within hippocampal tissues. Although these findings suggest an mTOR-dependent mechanism involving mitochondrial protection, the study did not investigate autophagy or mitophagy pathways, a limitation that should be addressed in future research. Collectively, these results demonstrate that Everolimus enhances cognitive function in 5 × FAD mice by promoting mitochondrial bioenergetics and mitigating oxidative stress, which positions it as a potential therapeutic candidate for cognitive dysfunction in Alzheimer's disease.
Insights
Everolimus, an mTOR inhibitor, improved cognitive function and spatial memory in Alzheimer
Area of Science:
- Neuroscience
- Pharmacology
- Aging Research
Background:
- Mammalian target of rapamycin (mTOR) inhibitors show potential in combating age-related diseases.
- The effects of Everolimus on cognitive function and its mechanisms are not fully understood.
- Alzheimer's disease is a major cause of cognitive dysfunction.
Purpose of the Study:
- To investigate the impact of Everolimus on cognitive abilities in a mouse model of Alzheimer's disease (5x FAD mice).
- To explore the underlying mechanisms by which Everolimus might affect cognitive function.
Main Methods:
- 5x FAD mice were administered varying doses of Everolimus via intraperitoneal injection every other day for 8 weeks.
- Cognitive abilities, including learning and spatial memory, were systematically evaluated.
- Hippocampal morphology and cell counts were analyzed post-treatment.
Main Results:
- Everolimus administration significantly improved learning and spatial memory in 5x FAD mice.
- Histological analysis revealed normal hippocampal morphology and an increased number of pyramidal cells.
- Improvements were linked to enhanced mitochondrial function, reduced oxidative stress, and better energy metabolism in hippocampal tissues.
Conclusions:
- Everolimus alleviates cognitive impairment in 5x FAD mice, suggesting a therapeutic potential for Alzheimer's disease.
- The drug enhances cognitive function by promoting mitochondrial bioenergetics and mitigating oxidative stress.
- Future research should explore the roles of autophagy and mitophagy in Everolimus's mechanism of action.
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