title: Autophagosomes accumulation is associated with β-amyloid deposits and secondary damage in the thalamus after focal cortical infarction in hypertensive rats.
abstract: Focal cerebral cortical infarction after distal middle cerebral artery occlusion causes β-amyloid deposition and secondary neuronal degeneration in the ipsilateral ventroposterior nucleus of the thalamus. Several studies suggest that autophagy is an active pathway for β-amyloid peptide generation. This study aimed to investigate the role of autophagy in thalamic β-amyloid deposition and neuronal degeneration after cerebral cortical infarction in hypertensive rats. At 7 and 14days after middle cerebral artery occlusion, neuronal death and β-amyloid deposits were evident in the ipsilateral ventroposterior nucleus, and the activity of β-site amyloid precursor protein (APP)-cleaving enzyme 1, required for β-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 β-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, β-amyloid deposits, and β-site APP-cleaving enzyme 1 activity. These results suggest that autophagosomes accumulate within thalamic cells after cerebral cortical infarction, which is associated with thalamic β-amyloid deposition and secondary neuronal degeneration via elevation of β-site APP-cleaving enzyme 1 level.
authors.affiliation: Department of Neurology and Stroke Center, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jingjing
authors.initials: J
authors.lastname: Li
authors.forename: Shihui
authors.initials: S
authors.lastname: Xing
authors.forename: Chuo
authors.initials: C
authors.lastname: Li
authors.forename: Yiliang
authors.initials: Y
authors.lastname: Li
authors.forename: Chao
authors.initials: C
authors.lastname: Dang
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Fan
authors.forename: Jian
authors.initials: J
authors.lastname: Yu
authors.forename: Zhong
authors.initials: Z
authors.lastname: Pei
authors.forename: Jinsheng
authors.initials: J
authors.lastname: Zeng
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000096:biosynthesis / Q000502:physiology; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000096:biosynthesis / Q000502:physiology; D001343:Autophagy / Q000502:physiology*; D002544:Cerebral Infarction / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D006973:Hypertension / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009410:Nerve Degeneration / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D010588:Phagosomes / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D058225:Plaque, Amyloid / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013788:Thalamus / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*
chemical_list: D016229:Amyloid beta-Peptides; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509281:Bace1 protein, rat