Age-related changes in cerebral blood vessels influencing cognitive ability in SAMP8 mouse models of AD / 中华神经医学杂志

ABSTRACT

Objective To explore the influence of age-related changes in the cerebral blood vessels (cerebral blood flow,blood-brain barrier integrity,and level of glucose transporter [GLUT]) in cognitive ability of SAMP8 mouse models of AD. Methods Ten SAMP8 mice and 10 homologous anti-senescence accelerated mice R1 (SAMR1) were chosen in our study; spatial learning and memory abilities of these mice were assessed using Morris water maze; cerebral blood flow was determined by laser Doppler flowmeter; blood-brain barrier (BBB) permeability was examined by fluorescence spectrophotometer; and expressions of GLUT1 and GLUT3 were determined using Western blotting.Results The cognitive abilities of SAMP8 mice damaged apparently even at 4 months of age as compared with those of SAMR1 mice, showing rigid thinking pattern and slow learning process in their Morris water maze test. With increasing of age, much obvious decrement in cerebral blood flow and severe BBB leakage was observed in SAMP8 mice; moreover, alterations in GLUT1 and GLUT3 expressions in the cortex and hippocampus of SAMP8 mice were observed. The cerebral blood flow,BBB integrity,and expressions of GLUT1 and GLUT3 were significantly affected by age and strain,and closely associated with cognitive abilities. Conclusion The alterations in cerebral blood flow and energy failure induced by aging and vascular insults are the reasons for neuron dysfunction and cognitive impairment in mice models of AD.