title: Stromal cell-derived factor 1α decreases β-amyloid deposition in Alzheimer's disease mouse model.
abstract: β-amyloid (Aβ) aggregates are known to induce neuronal and synaptic dysfunction, and thus are involved in learning and memory deficits in Alzheimer's disease (AD), making Aβ deposits a potential target for prevention or treatment. Microglia, especially bone marrow-derived microglia (BMDM), has been recently thought to play important roles in internalizing and phagocytozing Aβ. BMDM originate in the bone marrow, migrate into the blood as hematopoietic progenitor cells (HPCs) and enter the brain in a chemokine-dependent manner. An effective chemoattractant for HPCs is stromal cell-derived factor 1 (SDF-1), which is also involved in regulating HPCs differentiation. Therefore, we hypothesize that SDF-1 might have influence on the migration of BMDM from peripheral cycle to brain. To explore whether treatment with SDF-1α can decrease Aβ burden, APP/PS1 double transgenic mice were given intracerebroventricular injection of SDF-1α weekly from the age of 28 to 32 weeks (4 weeks of injections) or from 28 to 36 weeks (8 weeks of injections). The results of our study showed that SDF-1α treatment decreased the area and the number of Aβ deposits, increased the level of Iba-1, a marker of microglia, and increased the number of plaque associated microglia in the parenchyma of APP/PS1 transgenic mice. These results suggest that SDF-1 could provide a novel and promising target for the purpose of lowering Aβ pathology in AD.
authors.affiliation: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Xu
authors.forename: Jin-Cao
authors.initials: JC
authors.lastname: Chen
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Qin
authors.forename: Mao
authors.initials: M
authors.lastname: Liu
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Min-Jie
authors.initials: MJ
authors.lastname: Xie
authors.forename: Zhi-Yuan
authors.initials: ZY
authors.lastname: Yu
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhu
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D054377:Chemokine CXCL12 / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007276:Injections, Intraventricular; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D009154:Mutation / Q000235:genetics; D010446:Peptide Fragments; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D053764:Presenilin-1 / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D054377:Chemokine CXCL12; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)