title: Alpha7 nicotinic acetylcholine receptor is required for amyloid pathology in brain endothelial cells induced by Glycoprotein 120, methamphetamine and nicotine.
abstract: One of the most challenging issues in HIV-associated neurocognitive disorders (HAND) caused by HIV-1 virotoxins and drug abuse is the lack of understanding the underlying mechanisms that are commonly associated with disorders of the blood-brain barrier (BBB), which mainly consists of brain microvascular endothelial cells (BMEC). Here, we hypothesized that Glycoprotein 120 (gp120), methamphetamine (METH) and nicotine (NT) can enhance amyloid-beta (Aβ) accumulation in BMEC through Alpha7 nicotinic acetylcholine receptor (α7 nAChR). Both in vitro (human BMEC) (HBMEC) and in vivo (mice) models of BBB were used to dissect the role of α7 nAChR in up-regulation of Aβ induced by gp120, METH and NT. Aβ release from and transport across HBMEC were significantly increased by these factors. Methyllycaconitine (MLA), an antagonist of α7 nAChR, could efficiently block these pathogenic effects. Furthermore, our animal data showed that these factors could significantly increase the levels of Aβ, Tau and Ubiquitin C-Terminal Hydrolase L1 (UCHL1) in mouse cerebrospinal fluid (CSF) and Aβ in the mouse brains. These pathogenicities were significantly reduced by MLA, suggesting that α7 nAChR may play an important role in neuropathology caused by gp120, METH and NT, which are the major pathogenic factors contributing to the pathogenesis of HAND.
authors.affiliation: Department of Pediatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.|Saban Research Institute, Childrens Hospital Los Angeles, University of Southern California, Los Angeles, CA90027, USA.
authors.forename: Liqun
authors.initials: L
authors.lastname: Liu
authors.affiliation: Saban Research Institute, Childrens Hospital Los Angeles, University of Southern California, Los Angeles, CA90027, USA.|School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Yu
authors.affiliation: School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, 510515, China.|Department of Clinical Laboratory, Kunming Children's Hospital, Kunming Medical University, Kunming, Yunnan 650034, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Saban Research Institute, Childrens Hospital Los Angeles, University of Southern California, Los Angeles, CA90027, USA.|School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Bao
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
authors.forename: Lingjuan
authors.initials: L
authors.lastname: Liu
authors.affiliation: Saban Research Institute, Childrens Hospital Los Angeles, University of Southern California, Los Angeles, CA90027, USA.
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Wu
authors.affiliation: Saban Research Institute, Childrens Hospital Los Angeles, University of Southern California, Los Angeles, CA90027, USA.
authors.forename: Ambrose
authors.initials: A
authors.lastname: Jong
authors.affiliation: Department of Pediatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
authors.forename: Ding-An
authors.initials: DA
authors.lastname: Mao
authors.affiliation: Saban Research Institute, Childrens Hospital Los Angeles, University of Southern California, Los Angeles, CA90027, USA.|School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Sheng-He
authors.initials: SH
authors.lastname: Huang
mesh_terms: D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid / Q000473:pathology; D000682:Amyloid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D008694:Methamphetamine / Q000494:pharmacology*; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D021381:Protein Transport / Q000187:drug effects; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism; D009418:S100 Proteins / Q000378:metabolism; D013997:Time Factors; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D015415:Biomarkers; D015699:HIV Envelope Protein gp120; D000067759:Receptor for Advanced Glycation End Products; D009418:S100 Proteins; D064569:alpha7 Nicotinic Acetylcholine Receptor; C054634:methyllycaconitine; D008694:Methamphetamine; D009538:Nicotine; D000157:Aconitine