title: Everolimus (RAD001) ameliorates vascular cognitive impairment by regulating microglial function via the mTORC1 signaling pathway.
abstract: Vascular dementia (VaD) is a widely prevalent and devastating disease. Despite the tremendous complexity that limits understanding of the pathophysiology of VaD, microglial dysfunction has been attributed, in part, to immune microenviroment disorder and finally leads to cognitive deficits. Considered the mammalian target of rapamycin complex 1 (mTORC1) is a key player in regulation of glial function, our work focused on whether the mTOR inhibitor everolimus (RAD001) could overcome the destructive microglial function, change the phenotype and ameliorate cognitive decline induced by chronic cerebral hypoperfusion. Strikingly, the results suggest that inhibition of the mTORC1 activity by RAD001 ameliorates VaD by restoring microglia's M1/M2 balance. Therefore, RAD001 may have promise as a therapy for VaD disease.
authors.affiliation: Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China; Department of Neurology, Tianjin Huanhu Hospital, Tianjin 300060, China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Daojing
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Nong
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Ruiqiong
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Han
authors.affiliation: Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Changjuan
authors.initials: C
authors.lastname: Wei
authors.affiliation: Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Haijie
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Neurology, Tianjin Huanhu Hospital, Tianjin 300060, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China. Electronic address: hjw@tmu.edu.cn.
authors.forename: Junwei
authors.initials: J
authors.lastname: Hao
mesh_terms: D000818:Animals; D060825:Cognitive Dysfunction / Q000188:drug therapy* / Q000378:metabolism; D015140:Dementia, Vascular / Q000188:drug therapy* / Q000378:metabolism; D000068338:Everolimus / Q000494:pharmacology / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects* / Q000502:physiology; D046912:Multiprotein Complexes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D007166:Immunosuppressive Agents; D046912:Multiprotein Complexes; D000068338:Everolimus; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases
keywords: Chronic cerebral hypoperfusion; Cognitive deficits; M1/M2 balance; RAD001; mTOR pathway