title: Age-related alteration in cerebral blood flow and energy failure is correlated with cognitive impairment in the senescence-accelerated prone mouse strain 8 (SAMP8).
abstract: Cerebrovascular dysfunction is an early pathogenic event in Alzheimer's disease (AD) and plays a key role in the disease process. Cerebral hypoperfusion, brain glucose hypometabolism and disrupted blood-brain barrier (BBB) integrity contributed to the onset and progression of AD. However, the relationships between the age-related cognitive impairment and cerebral blood flow (CBF), energy metabolism and BBB have not been clearly explained. In this study, we investigated the cognitive function, CBF, BBB damage and expression level of glucose transporter (GLUT) 1 and 3 of senescence-accelerated mouse prone 8 (SAMP8), and the correlations between each of them were analyzed. When compared with SAMR1 (senescence-accelerated mouse resistant 1), the cognitive abilities of SAMP8 were damaged apparently even at 4 months of age, showing up a slower and more capricious acquisition in Morris water maze tasks. In both SAMP8 and SAMR1, reduced CBF and increased BBB leakage were observed with increasing age, but an earlier and more severe impairment was detected in SAMP8. In addition, alterations of GLUT1 and GLUT3 protein expression in cortex and hippocampus were more prominent in SAMP8. Correlation analysis demonstrated that the increased escape latency was correlated negatively with CBF and expression of glucose transporters; and positively with BBB permeability in the hippocampus. These results suggested that CBF, BBB integrity, the expression of GLUT1 and GLUT3 were significantly affected by age and strain, which were also closely associated with cognitive ability. The alteration in CBF and energy failure induced by aging and vascular insults resulted in cognitive decline in SAMP8.
authors.affiliation: First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China, zhangxuezhu1999@yahoo.com.cn.
authors.forename: Xuezhu
authors.initials: X
authors.lastname: Zhang
authors.forename: Guomin
authors.initials: G
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Guo
authors.forename: Kun
authors.initials: K
authors.lastname: Nie
authors.forename: Yujie
authors.initials: Y
authors.lastname: Jia
authors.forename: Lan
authors.initials: L
authors.lastname: Zhao
authors.forename: Jianchun
authors.initials: J
authors.lastname: Yu
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001812:Blood-Brain Barrier / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000098:blood supply* / Q000503:physiopathology; D003072:Cognition Disorders / Q000503:physiopathology*; D004195:Disease Models, Animal; D004734:Energy Metabolism; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains
chemical_list: D051246:Glucose Transport Proteins, Facilitative
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