• Jing He, Yan Huang, Guo Du, Zhiqiang Wang, Yang Xiang, and Qingsong Wang.
• Department of Neurology, the General Hospital of Western Theater Command, Chengdu 610083, China.
• Neuroscience. 2019 Sep 1; 415: 215-229.

ObjectiveChronic cerebral hypoperfusion (CCH) is an important pathophysiological basis for AD and vascular cognitive impairment (VCI), but the underlying mechanisms are not completely clear. Age-related mitochondrial aging-like changes were closely associated with nervous system diseases and ischemia. This study aimed to observe the changes of cognitive function and hippocampal mitochondrial aging in rats with CCH.MethodsHealthy male SD rats were randomly divided into CCH group and sham group, and then were randomly divided into four subgroups [1-, 4-, 12- and 24-week (W) groups]. The cognitive function of rats was detected by the Open field, Object recognition and Morris water maze tests. The mitochondrial structure was observed under electron microscope. The mitochondrial alpha-synuclein was detected by western blotting and immunofluorescence, and the MtDNA4834bp deletion and the PGC-1alpha levels were detected by PCR in the hippocampus of rats.ResultsThe lasting spatial learning and memory deficits were more obvious in CCH group. The mitochondrial shape, cristae and vacuolation showed more obvious damage in CCH group. Mitochondrial DNA4834bp deletion rate in CCH group was significantly increased at 4W and 12W with decreased abnormality, and PGC-1α was increased at each time points, wherein the 12W group showed significant increase. The mitochondrial alpha-synuclein in CCH group was increased more obviously. The increase of alpha-synuclein in the hippocampal DG in CCH group was more obvious.ConclusionsCCH induced long-term spatial learning and memory deficits. The related alterations of mitochondrial aging and alpha-synuclein in the hippocampus are crucial for VCI pathogenesis.Copyright © 2019. Published by Elsevier Ltd.

31 keywords...

hide…