title: Triggering receptor expressed on myeloid cells 2 knockdown exacerbates aging-related neuroinflammation and cognitive deficiency in senescence-accelerated mouse prone 8 mice.
abstract: As a major characteristic of aging process, neuroinflammation is involved in the pathogenesis of several aging-related diseases including Alzheimer's disease (AD). Triggering receptor expressed on myeloid cells 2 (TREM2) is a newly identified risk gene for AD, which regulates inflammatory process in peripheral tissues via modulating the release of inflammatory cytokines. However, the role of TREM2 in aging-related neuroinflammation, cognitive deficiency, and AD-like neuropathology is unclear so far. Here, we detected the protein levels of TREM2 in brain of 3-, 7-, and 11-month-old senescence-accelerated mouse prone 8 (SAMP8) mice and observed that TREM2 levels were increased during aging process. We then knocked down TREM2 expression in brain of SAMP8 mice by nonviral RNA interference and found a significant increase in proinflammatory cytokines including tumor necrosis factor-α and interleukin (IL)-6, which was accompanied by a reduction in IL-10. Meanwhile, more obvious neuronal and synaptic losses and cognitive impairment were observed. These findings indicate that TREM2 may play a protective role against aging-related neuroinflammation and cognitive impairment.
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Teng
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, People's Republic of China; Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, People's Republic of China; Department of Neurology, Qingdao Municipal Hospital, College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, People's Republic of China. Electronic address: yu-jintai@163.com.
authors.forename: Jin-Tai
authors.initials: JT
authors.lastname: Yu
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Xi-Chen
authors.initials: XC
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, People's Republic of China.
authors.forename: Meng-Shan
authors.initials: MS
authors.lastname: Tan
authors.affiliation: The Clinical Laboratory of Wuxi Mental Health Center, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Li-Ze
authors.initials: LZ
authors.lastname: Gu
authors.affiliation: Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Ying-Dong
authors.initials: YD
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, People's Republic of China; Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, People's Republic of China; Department of Neurology, Qingdao Municipal Hospital, College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, People's Republic of China. Electronic address: dr.tanlan@163.com.
authors.forename: Lan
authors.initials: L
authors.lastname: Tan
mesh_terms: D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D000818:Animals; D001921:Brain / Q000378:metabolism; D003072:Cognition Disorders / Q000235:genetics* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008818:Mice, Neurologic Mutants; D009474:Neurons / Q000473:pathology; D034741:RNA, Small Interfering; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D013569:Synapses / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; D011971:Receptors, Immunologic; C498716:Trem2 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10
keywords: Aging; Alzheimer's disease; Cognitive deficiency; Neuroinflammation; SAMP8; SAMR1; TREM2