Cerebrovascular hypoperfusion induces spatial memory impairment, synaptic changes, and amyloid-β oligomerization in rats.
Cerebrovascular hypoperfusion occurs prior to the clinical symptoms of Alzheimer's disease (AD) and represents the most accurate indicator predicting whether an individual develops AD at a future time. To study how cerebrovascular hypoperfusion contributes to AD, we induced cerebrovascular hypoperfusion by bilateral carotid occlusion surgery in adult rats and investigated its impacts on spatial memory, synapses, and accumulation of oligomeric amyloid-β. We found progressive spatial memory deficits, as tested by Morris water maze, starting 30 days after occlusion surgery. The memory deficits were accompanied with decrease in synaptic density and alterations of synaptic ultrastructure in the CA1 area of the hippocampus, as evaluated by electron microscopy. By using immunoelectron microscopy, we also found time-dependent accumulation of oligomeric amyloid-β in the hippocampus, especially in the axonal terminals after chronic cerebrovascular hypoperfusion. Western blot analysis revealed decreased levels of postsynaptic density-95 (PSD-95) and synaptophysin in rat brains after chronic cerebrovascular hypoperfusion. Our findings provide novel insight into the mechanism by which chronic cerebrovascular hypoperfusion contributes to the pathogenesis of AD.
Wang
Xiaojuan
X
Department of Pathology, Capital Medical University, Beijing, China.
Xing
Anfeng
A
Xu
Changlei
C
Cai
Qing
Q
Liu
Hong
H
Li
Liang
L
D000544:Alzheimer Disease / Q000209:etiology* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002561:Cerebrovascular Disorders / Q000473:pathology*; D000076122:Disks Large Homolog 4 Protein; D006624:Hippocampus / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D018782:Maze Learning; D008565:Membrane Proteins / Q000378:metabolism; D008569:Memory Disorders / Q000209:etiology / Q000473:pathology; D016253:Microscopy, Immunoelectron; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000473:pathology*; D016708:Synaptophysin / Q000378:metabolism; D013997:Time Factors
D016229:Amyloid beta-Peptides; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D016708:Synaptophysin