Autophagosomes accumulation is associated with ß-amyloid deposits and secondary damage in the thalamus after focal cortical infarction in hypertensive rats

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.