Chronic cerebral hypoperfusion in a mouse model of Alzheimer's disease: an additional contributing factor of cognitive impairment.
The purpose of the present study was to evaluate whether chronic cerebral hypoperfusion would affect cognitive status in an Alzheimer mouse model. Behavioral tests and histological evaluations were performed using female Tg2576 mice eight weeks after right common carotid artery occlusion (rCCAO), which is known to induce a type of vascular dementia without neuronal necrosis in nontransgenic mice. Positron emission tomography with (18)F-fluorodeoxyglucose (FDG-PET) was utilized to evaluate metabolic status in the rCCAO-operated brain of nontransgenic mice. Escape latency from the Morris water maze test was not significantly different between rCCAO- and sham-operated mice. However, the learning curve was impaired in rCCAO-operated transgenic mice while it was preserved in sham-operated transgenic or rCCAO-operated nontransgenic mice. Histological examination revealed no evidence of cell death in the rCCAO-operated brains, and the extent of amyloid deposition was not different in rCCAO- and sham-operated mice. The brain of rCCAO-operated mice showed metabolic deficits in the ipsilateral parietal cortex through FDG-PET. In conclusion, further cognitive decline which is more comparable to typical Alzheimer's disease was induced by chronic cerebral hypoperfusion in an Alzheimer mouse model. This aggravation might be associated with hypometabolism via chronic cerebral hypoperfusion.
Department of Neurology, Ajou University School of Medicine, San-5, Wonchondong, Suwon 442-749, South Korea.
Jin Soo
JS
Lee
Doo Soon
DS
Im
Young-Sil
YS
An
Ji Man
JM
Hong
Byoung Joo
BJ
Gwag
In Soo
IS
Joo
D000544:Alzheimer Disease / Q000209:etiology / Q000503:physiopathology* / Q000523:psychology; D000818:Animals; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications* / Q000503:physiopathology; D016893:Carotid Stenosis / Q000150:complications; D002560:Cerebrovascular Circulation; D003072:Cognition Disorders / Q000209:etiology / Q000503:physiopathology* / Q000523:psychology; D015140:Dementia, Vascular / Q000209:etiology / Q000503:physiopathology / Q000523:psychology; D005260:Female; D005947:Glucose / Q000378:metabolism; D018782:Maze Learning; D008570:Memory, Short-Term; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013045:Species Specificity
D005947:Glucose