Alpha7 nicotinic acetylcholine receptor is required for amyloid pathology in brain endothelial cells induced by Glycoprotein 120, methamphetamine and nicotine

作者：Liu, Liqun; Yu, Jingyi; Li, Li; Zhang, Bao; Liu, Lingjuan; Wu, Chun-Hua; Jong, Ambrose; Mao, Ding-An^*; Huang, Sheng-He^*

来源：Scientific Reports, 2017, 7(1): 40467.

DOI：10.1038/srep40467

• SYNAPTIC PLASTICITY
• A-BETA
• HIV
• BARRIER
• PLASMA
• GP120
• AMYLOID-BETA(1-42)
• NEUROTOXICITY
• ACCUMULATION
• PATHOGENESIS

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 (A beta) accumulation in BMEC through Alpha7 nicotinic acetylcholine receptor (alpha 7 nAChR). Both in vitro (human BMEC) (HBMEC) and in vivo (mice) models of BBB were used to dissect the role of alpha 7 nAChR in up-regulation of A beta induced by gp120, METH and NT. A beta release from and transport across HBMEC were significantly increased by these factors. Methyllycaconitine (MLA), an antagonist of alpha 7 nAChR, could efficiently block these pathogenic effects. Furthermore, our animal data showed that these factors could significantly increase the levels of A beta, Tau and Ubiquitin C-Terminal Hydrolase L1 (UCHL1) in mouse cerebrospinal fluid (CSF) and A beta in the mouse brains. These pathogenicities were significantly reduced by MLA, suggesting that a7 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.

• 出版日期2017-1-11
• 单位南方医科大学; 昆明医科大学; 中南大学