期刊
JOURNAL OF NEUROCHEMISTRY
卷 120, 期 4, 页码 564-573出版社
WILEY
DOI: 10.1111/j.1471-4159.2011.07496.x
关键词
3-methyladenine; ss-amyloid; ss-secretase; autophagy; cerebral infarction; rats
资金
- National Basic Research Program of China [2011CB707805]
- National Natural Science Foundation of China [39940012, 30973108, 81000500, U1032005]
- Medical Science Foundation of Guangdong Province of China [B2010081]
- Department of Education of Guangdong Province
- Bureau for Science and Information Technology of Guangzhou
Focal cerebral cortical infarction after distal middle cerebral artery occlusion causes beta-amyloid deposition and secondary neuronal degeneration in the ipsilateral ventroposterior nucleus of the thalamus. Several studies suggest that autophagy is an active pathway for beta-amyloid peptide generation. This study aimed to investigate the role of autophagy in thalamic beta-amyloid deposition and neuronal degeneration after cerebral cortical infarction in hypertensive rats. At 7 and 14 days after middle cerebral artery occlusion, neuronal death and beta-amyloid deposits were evident in the ipsilateral ventroposterior nucleus, and the activity of beta-site amyloid precursor protein (APP)-cleaving enzyme 1, required for beta-amyloid peptide generation, was elevated in the thalamus. In correlation, both the number of cells showing punctate microtubule-associated protein 1A light chain 3 fluorescence and levels of light chain 3-II protein, an autophagosome marker, were markedly increased. Notably, most of the cells that over-expressed beta-site APP-cleaving enzyme 1 displayed punctate light chain 3 staining. Furthermore, the inhibition of autophagy with 3-methyladenine significantly reduced the thalamic neuronal damage, beta-amyloid deposits, and beta-site APP-cleaving enzyme 1 activity. These results suggest that autophagosomes accumulate within thalamic cells after cerebral cortical infarction, which is associated with thalamic beta-amyloid deposition and secondary neuronal degeneration via elevation of beta-site APP-cleaving enzyme 1 level.
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