title: Temporal changes of CD68 and α7 nicotinic acetylcholine receptor expression in microglia in Alzheimer's disease-like mouse models.
abstract: We previously reported that activated microglia are involved in amyloid-β (Aβ) clearance and that stimulation of α7 nicotinic acetylcholine receptors (nAChR) in microglia enhances Aβ clearance. Nevertheless, how microglia and α7 nAChR in microglia are affected in Alzheimer's disease (AD) remains unknown. The present study aimed to collect fundamental data for considering whether microglia are potential targets for AD treatment and the appropriate timing of therapeutic intervention, by evaluating the temporal changes of Aβ, microglia, neurons, presynapses, and α7 nAChR by immunohistochemical studies in mouse models of AD. In an Aβ-injected AD mouse model, we observed early accumulation of CD68-positive microglia at Aβ deposition sites and gradual reduction of Aβ. Microglia were closely associated with Aβ deposits, and were confirmed to participate in clearing Aβ. In a transgenic mouse model of AD, we observed an increase in Aβ deposition from 6 months of age, followed by a gradual increase in microglial accumulation at Aβ deposit sites. Activated microglia in APdE9 mice showed two-step transition: a CD68-negative activated form at 6-9 months and a CD68-positive form from 12 months of age. In addition, α7 nAChR in microglia increased markedly at 6 months of age when activated microglia appeared for the first time, and decreased gradually coinciding with the increase of Aβ deposition. These findings suggest that early microglial activation is associated with α7 nAChR upregulation in microglia in APdE9 mice. These novel findings are important for the development of new therapeutic strategy for AD.
authors.affiliation: Department of Neurology, School of Medicine, Sapporo Medical University, Sapporo, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Matsumura
authors.affiliation: Department of Neurology, School of Medicine, Sapporo Medical University, Sapporo, Japan.
authors.forename: Syuuichirou
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Department of Neurology, School of Medicine, Sapporo Medical University, Sapporo, Japan.
authors.forename: Naotoshi
authors.initials: N
authors.lastname: Iwahara
authors.affiliation: Department of Neurology, School of Medicine, Sapporo Medical University, Sapporo, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Hisahara
authors.affiliation: Department of Neurology, School of Medicine, Sapporo Medical University, Sapporo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kawamata
authors.affiliation: Department of Neurology, School of Medicine, Sapporo Medical University, Sapporo, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Department of Neurology, School of Medicine, Sapporo Medical University, Sapporo, Japan.
authors.forename: Ayano
authors.initials: A
authors.lastname: Yamauchi
authors.affiliation: Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Kyoto, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Takata
authors.affiliation: Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Kyoto, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kitamura
authors.affiliation: Department of Neurology, School of Medicine, Sapporo Medical University, Sapporo, Japan.
authors.forename: Shun
authors.initials: S
authors.lastname: Shimohama
mesh_terms: D000375:Aging / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D010784:Photomicrography; D058225:Plaque, Amyloid / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism; D013997:Time Factors; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000378:metabolism*; D000097382:CD68 Molecule
chemical_list: D016229:Amyloid beta-Peptides; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; D010446:Peptide Fragments; D016708:Synaptophysin; D064569:alpha7 Nicotinic Acetylcholine Receptor; C491049:Aif1 protein, mouse; C081026:CD68 protein, mouse; D000097382:CD68 Molecule; C569015:Syp protein, mouse; C075222:amyloid beta-protein (1-42)
keywords: Alzheimer's disease; CD68; amyloid-β; hippocampus; injections; microglia; phagocytosis; temporal; transgenic; α7 nAChR