Inhibition of autophagy attenuates cognitive decline and mitochondrial dysfunction in an Alzheimer's disease mouse model with chronic cerebral hypoperfusion.
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引用次数: 0
Abstract
This study aimed to investigate the impact of chronic cerebral hypoperfusion (CCH) on cognitive function, amyloid-β (Aβ) deposition, cellular autophagy, and mitochondrial dynamics in an Alzheimer's disease (AD) mouse model, and to evaluate the intervention effects of autophagy modulation on these outcomes. Utilizing the APP/PS1 mouse model combined with CCH, we assessed cognitive function, Aβ deposition, and the expression levels of relevant proteins through behavioral tests and immunohistochemical analysis. Our findings revealed pronounced cognitive deficits and increased Aβ deposition in the AD + CCH group mice, along with upregulation of mitochondrial fission proteins (Drp1, Fis1) and downregulation of mitochondrial fusion proteins (Opa1, Mfn1), indicating a shift towards mitochondrial fission and promoting cell apoptosis. Additionally, alterations were observed in the expression levels of cellular autophagy-related proteins (LC3-II, P62), which were reversed by treatment with autophagic inhibitor 3-methyladenine (3-MA). Furthermore, the expression of mitochondrial autophagy-related proteins PINK1 and Parkin was affected, with 3-MA alleviating this effect. In summary, our study elucidates the complex interplay among cognitive decline, increased Aβ deposition, and mitochondrial dysfunction in the AD + CCH model, and suggests that modulating autophagy could be a potential therapeutic strategy for treating the AD + CCH model.
期刊介绍:
An international multidisciplinary journal devoted to fundamental research in the brain sciences.
Brain Research publishes papers reporting interdisciplinary investigations of nervous system structure and function that are of general interest to the international community of neuroscientists. As is evident from the journals name, its scope is broad, ranging from cellular and molecular studies through systems neuroscience, cognition and disease. Invited reviews are also published; suggestions for and inquiries about potential reviews are welcomed.
With the appearance of the final issue of the 2011 subscription, Vol. 67/1-2 (24 June 2011), Brain Research Reviews has ceased publication as a distinct journal separate from Brain Research. Review articles accepted for Brain Research are now published in that journal.