title: CCR5 deficiency accelerates lipopolysaccharide-induced astrogliosis, amyloid-beta deposit and impaired memory function.
abstract: Chemokine receptors are implicated in inflammation and immune responses. Neuro-inflammation is associated with activation of astrocyte and amyloid-beta (Aβ) generations that lead to pathogenesis of Alzheimer disease (AD). Previous our study showed that deficiency of CC chemokine receptor 5 (CCR5) results in activation of astrocytes and Aβ deposit, and thus memory dysfunction through increase of CC chemokine receptor 2 (CCR2) expression. CCR5 knockout mice were used as an animal model with memory dysfunction. For the purpose LPS was injected i.p. daily (0.25 mg/kg/day). The memory dysfunctions were much higher in LPS-injected CCR5 knockout mice compared to CCR5 wild type mice as well as non-injected CCR5 knockout mice. Associated with severe memory dysfuction in LPS injected CCR5 knockout mice, LPS injection significant increase expression of inflammatory proteins, astrocyte activation, expressions of β-secretase as well as Aβ deposition in the brain of CCR5 knockout mice as compared with that of CCR5 wild type mice. In CCR5 knockout mice, CCR2 expressions were high and co-localized with GFAP which was significantly elevated by LPS. Expression of monocyte chemoattractant protein-1 (MCP-1) which ligands of CCR2 also increased by LPS injection, and increment of MCP-1 expression is much higher in CCR5 knockout mice. BV-2 cells treated with CCR5 antagonist, D-ala-peptide T-amide (DAPTA) and cultured astrocytes isolated from CCR5 knockout mice treated with LPS (1 μg/ml) and CCR2 antagonist, decreased the NF-Ä¸B activation and Aβ level. These findings suggest that the deficiency of CCR5 enhances response of LPS, which accelerates to neuro-inflammation and memory impairment.
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Chul Ju
authors.initials: CJ
authors.lastname: Hwang
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Mi Hee
authors.initials: MH
authors.lastname: Park
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Jae Yeon
authors.initials: JY
authors.lastname: Hwang
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Ju Hwan
authors.initials: JH
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Na Young
authors.initials: NY
authors.lastname: Yun
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Sang Yeon
authors.initials: SY
authors.lastname: Oh
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Ju Kyung
authors.initials: JK
authors.lastname: Song
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Hyun Ok
authors.initials: HO
authors.lastname: Seo
authors.affiliation: College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Yun-Bae
authors.initials: YB
authors.lastname: Kim
authors.affiliation: College of Natural Resources and Life Science, Pusan National University, Pusan, Republic of Korea.
authors.forename: Dae Yeon
authors.initials: DY
authors.lastname: Hwang
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Ki-Wan
authors.initials: KW
authors.lastname: Oh
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Sang-Bae
authors.initials: SB
authors.lastname: Han
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
mesh_terms: D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology*; D001522:Behavior, Animal; D049109:Cell Proliferation; D002478:Cells, Cultured; D005911:Gliosis / Q000209:etiology* / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000150:complications*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D008569:Memory Disorders / Q000209:etiology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058225:Plaque, Amyloid / Q000209:etiology* / Q000473:pathology; D019713:Receptors, CCR5 / Q000502:physiology*
chemical_list: C000592874:CCR5 protein, mouse; D008070:Lipopolysaccharides; D019713:Receptors, CCR5
keywords: Alzheimer’s disease (AD); Amyloid beta (Aβ); CC chemokine receptor 2 (CCR2); CC chemokine receptor 5 (CCR5); Pathology Section; memory impairment