title: Mitochondrial bioenergetic deficits in the hippocampi of rats with chronic ischemia-induced vascular dementia.
abstract: Vascular dementia (VD), defined as a loss of memory and cognitive function resulting from vascular lesions in the brain, is the second-most-common cause of dementia in the elderly, after Alzheimer's disease. In recent years, research has focused on the pathogenesis of VD, and mitochondrial bioenergetic deficits have been suggested to contribute to VD onset. To further investigate the role of mitochondria in VD, we used a rat model of VD, which involved permanent bilateral occlusion of the common carotid arteries (with a 1-week interval between artery occlusion to avoid an abrupt reduction in cerebral blood flow) leading to chronic cerebral hypoperfusion. Prior to occlusion, male Wistar rats underwent 7 days of Morris water maze training. Only animals that could swim and passed the Morris water maze test were chosen for the study. After 5 days of Morris water maze training, mitochondria from the hippocampi of rats, which were randomly selected from animals that could complete the Morris water maze test, were isolated for functional assessment. Mitochondria isolated from the hippocampi of rats from the ischemia group had decreased pyruvate dehydrogenase protein levels, and increased oxidative stress, as manifested by increased hydrogen peroxide production. The ischemia group mitochondria also exhibited decreased respiration coupled to decreased expression and activity of the electron transport chain complex IV (cytochrome c oxidase). These results indicate that the mitochondrial oxidative metabolism is inhibited in the hippocampi of rats following chronic ischemia-induced VD. As the mitochondrial oxidative metabolism deficits, namely mitochondrial bioenergetic deficits directly affect the functions of neurons, it may contribute to VD onset.
authors.affiliation: Department of Vascular Surgery, China-Japan Union Hospital, No. 829 Xinmin Street, ChaoYang District, Jilin University, Changchun 130021, Jilin Province, People's Republic of China. djs3043@126.com
authors.forename: J
authors.initials: J
authors.lastname: Du
authors.forename: M
authors.initials: M
authors.lastname: Ma
authors.forename: Q
authors.initials: Q
authors.lastname: Zhao
authors.forename: L
authors.initials: L
authors.lastname: Fang
authors.forename: J
authors.initials: J
authors.lastname: Chang
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: R
authors.initials: R
authors.lastname: Fei
authors.forename: X
authors.initials: X
authors.lastname: Song
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D015140:Dementia, Vascular / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D003576:Electron Transport Complex IV / Q000378:metabolism; D004734:Energy Metabolism; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D011768:Pyruvate Dehydrogenase Complex; D006861:Hydrogen Peroxide; D003576:Electron Transport Complex IV