title: The Role of Autophagy in the Correlation Between Neuron Damage and Cognitive Impairment in Rat Chronic Cerebral Hypoperfusion.
abstract: Pathological changes and cognitive impairment caused by chronic cerebral hypoperfusion (CCH) have been previously reported. However, how these changes progress remains unclear. Additionally, there are few studies regarding the mechanism underlying the involvement of autophagy in these processes. Two-step bilateral common carotid artery occlusion (BCCAO) was performed to replicate CCH in Sprague Dawley rats. The animals were divided into seven groups, including a sham group and 2-, 4-, 8-, 12-, 16-, and 20-week BCCAO groups (n = 7 per group). Five additional rats were used to monitor cerebral blood fluid (CBF) changes via laser speckle contrast imaging (LSCI). We tested for cognitive changes and pathological changes, including neuronal injury, white matter lesions, and β-Amyloid (Aβ) deposition, via acknowledged methods. Autophagy was analyzed via western blotting and immunohistochemistry. Cognitive impairment appeared beginning at 8 weeks after BCCAO despite improvement in CBF. Neuronal damage began at 8 weeks in the hippocampal CA1 region and at 4 weeks in the cortex. White matter injury was detected in all BCCAO groups. Intracellular Aβ accumulation occurred earlier than extracellular plaque formation. The levels of autophagy-related proteins (Beclin-1, light chain 3B, and P62) increased beginning at 2 weeks in the cortex and at 4 weeks in the hippocampus and remained elevated throughout the remainder of the study period. Despite recovery of CBF, autophagy dysfunction occurred early after CCH and played an important role in neuronal deterioration, cognitive decline, and intracellular Aβ aggregation.
authors.affiliation: Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Xuhui District, Shanghai, 200233, China.
authors.forename: Wenying
authors.initials: W
authors.lastname: Zou
authors.affiliation: Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Xuhui District, Shanghai, 200233, China.
authors.forename: Yufei
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Xuhui District, Shanghai, 200233, China.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Xuhui District, Shanghai, 200233, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Xuhui District, Shanghai, 200233, China. xjzzhang@126.com.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Xuhui District, Shanghai, 200233, China. fujianliang@163.com.
authors.forename: Jianliang
authors.initials: J
authors.lastname: Fu
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D001343:Autophagy; D000071186:Beclin-1 / Q000378:metabolism; D056547:CA1 Region, Hippocampal / Q000473:pathology / Q000503:physiopathology; D017536:Carotid Artery, Common / Q000473:pathology / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D003072:Cognition Disorders / Q000473:pathology* / Q000503:physiopathology*; D021621:Imaging, Three-Dimensional; D008297:Male; D008568:Memory; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D017207:Rats, Sprague-Dawley; D066127:White Matter / Q000473:pathology / Q000503:physiopathology
chemical_list: D016229:Amyloid beta-Peptides; D034961:Antigens, Nuclear; D000071186:Beclin-1; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; C526109:Anxa3 protein, rat; C546339:Rbfox3 protein, rat
keywords: Autophagy; Cerebral blood flow; Chronic cerebral hypoperfusion; Cognitive impairment; β-Amyloid