Changed clathrin regulatory proteins in the brains of Alzheimer's disease patients and animal models.
In the study, the expression of clathrin regulatory proteins dynamin I, AP180, and synaptic vesicle protein synaptophysin in multiple brain regions of the patients with Alzheimer's disease (AD), the transgenic mice carrying the Swedish mutation of amyloid-β protein precursor (AβPP) 670/671 (AβPPSWE), and the rats injected by bilateral hippocampus with amyloid-β peptide (Aβ)1-42 were examined by immunohistochemistry and Nissl staining, Western blotting, and Real-time PCR, respectively. Spatial learning and memory of the rats were evaluated by Morris Water Maze test, and the ability of endocytosis in the cultured rat hippocampal neurons was detected by FM1-43 fluorescence imaging. Significant decreases in protein levels of dynamin I, AP180, and synaptophysin were observed in both AD patients and mice with AβPPSWE as compared to controls. Obvious declines of dynamin I and synaptophysin at protein and mRNA levels and impaired learning and spatial memory ability were found in the rats injected with Aβ1-42 as compared to controls. In addition, deposits of Aβ localized in the hippocampus around the sites of Aβ1-42 injection and the decreased numbers of Nissl bodies in neurons were found. Moreover, the disrupted synaptic vesicle endocytosis and decreased dynamin I protein were detected in stimulated hippocampal neurons treated with Aβ1-42. These findings imply a malfunctioning clathrin-mediated endocytosis during AD pathological processes, which might be relevant to the mechanism underlying the cognitive deficit associated with AD.
Cao
Ying
Y
Department of Pathology, Guiyang Medical University, Guiyang, China.
Xiao
Yan
Y
Ravid
Rivka
R
Guan
Zhi-Zhong
ZZ
D033942:Adaptor Proteins, Vesicular Transport / Q000096:biosynthesis / Q000502:physiology*; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D002478:Cells, Cultured; D002966:Clathrin / Q000037:antagonists & inhibitors / Q000502:physiology*; D004195:Disease Models, Animal; D034284:Dynamin I / Q000037:antagonists & inhibitors / Q000502:physiology*; D004705:Endocytosis / Q000235:genetics; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D034041:Monomeric Clathrin Assembly Proteins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016708:Synaptophysin / Q000502:physiology*
D033942:Adaptor Proteins, Vesicular Transport; D016564:Amyloid beta-Protein Precursor; D002966:Clathrin; D034041:Monomeric Clathrin Assembly Proteins; D016708:Synaptophysin; C439023:clathrin assembly protein AP180; D034284:Dynamin I