title: Cerebral microemboli increase β-amyloid protein deposition, MMP-9, and GFAP expression in the Alzheimer`s model of APP/PS1 double transgenic mice.
abstract: We investigated the effects of cerebral arterial microemboli on amyloid β protein (Aβ) deposition in the hippocampal region of amyloid precursor protein/presenilin 1 (APP/PS1) double transgenic mice and evaluated the role of cerebral arterial microemboli in Alzheimer's disease (AD) pathogenesis. The mice were divided into a wild-type sham surgery group (n = 15), a wild-type coupled with microemboli group (n =15), an APP/PS1 double transgenic sham surgery group (n =15) and an APP/PS1 double transgenic coupled with microemboli group (n =15). The microemboli mice were injected via the left internal carotid artery with 300 µL of a normal saline suspension containing 100 whole blood clot-derived microemboli (25-50 µm). The sham surgery mice were injected with equal volumes of saline. After the mouse model was established for 1, 2 or 4 weeks, the Aβ1-42 deposition in the left hippocampal region and the matrix metalloproteinase-9 (MMP-9) and glial fibrillary acidic protein (GFAP) expression levels were determined through immunohistochemical staining. The Aβ1-42 deposition level in the left hippocampi of transgenic microemboli group was significantly greater than in the transgenic sham group at week 1 and 2 (P<0.001) but not at week 4. No Aβ1-42 deposition was detected in the wild-type groups. Only sporadic MMP-9- and GFAP-positive cells were observed in the wild-type sham group. Significantly more MMP-9- and GFAP-positive cells were detected in the transgenic groups (P<0.001), particularly in the transgenic microemboli group. An intragroup analysis of the time factor for the microemboli groups showed significantly more MMP-9- and GFAP-positive cells at week 1 than at week 2 or 4 (P<0.001). No difference was detected between time points in the sham groups. Cerebral microemboli increased Aβ deposition in the hippocampal region of APP/PS1 double transgenic mice. MMP-9 and GFAP expression may play an important role in excess Aβ deposition, which is caused by an imbalance between the protein's synthesis and removal.
authors: Min
authors: M
authors: Ning
authors: Yiying
authors: Y
authors: Wu
authors: Xiushi
authors: X
authors: Ni
authors: Yanling
authors: Y
authors: Zhao
authors: Department of Geriatrics, Shanghai First People's Hospital, Shanghai Jiao Tong University, No. 100 Haining Road, Shanghai 200080, China. drnixiushi@yeah.net.
authors: Rujing
authors: R
authors: Ling
mesh_terms: D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D020766:Intracranial Embolism / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D010446:Peptide Fragments / Q000378:metabolism*; D053764:Presenilin-1 / Q000235:genetics; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D005904:Glial Fibrillary Acidic Protein; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; C075222:amyloid beta-protein (1-42); D020780:Matrix Metalloproteinase 9