| First Author | Zhang B | Year | 2015 |
| Journal | BMC Infect Dis | Volume | 15 |
| Pages | 352 | PubMed ID | 26285576 |
| Mgi Jnum | J:328386 | Mgi Id | MGI:6851689 |
| Doi | 10.1186/s12879-015-1075-9 | Citation | Zhang B, et al. (2015) Alpha7 nicotinic acetylcholine receptor is required for blood-brain barrier injury-related CNS disorders caused by Cryptococcus neoformans and HIV-1 associated comorbidity factors. BMC Infect Dis 15:352 |
| abstractText | BACKGROUND: Cryptococcal meningitis is the most common fungal infection of the central nervous system (CNS) in HIV/AIDS. HIV-1 virotoxins (e.g., gp41) are able to induce disorders of the blood-brain barrier (BBB), which mainly consists of BMEC. Our recent study suggests that alpha7 nAChR is an essential regulator of inflammation, which contributes to regulation of NF-kappaB signaling, neuroinflammation and BBB disorders caused by microbial (e.g., HIV-1 gp120) and non-microbial [e.g., methamphetamine (METH)] factors. However, the underlying mechanisms for multiple comorbidities are unclear. METHODS: In this report, an aggravating role of alpha7 nAChR in host defense against CNS disorders caused by these comorbidities was demonstrated by chemical [inhibitor: methyllycaconitine (MLA)] and genetic (alpha7(-/-) mice) blockages of alpha7 nAChR. RESULTS: As shown in our in vivo studies, BBB injury was significantly reduced in alpha7(-/-) mice infected with C. neoformans. Stimulation by the gp41 ectodomain peptide (gp41-I90) and METH was abolished in the alpha7(-/-) animals. C. neoformans and gp41-I90 could activate NF-kappaB. Gp41-I90- and METH-induced monocyte transmigration and senescence were significantly inhibited by MLA and CAPE (caffeic acid phenethyl ester, an NF-kappaB inhibitor). CONCLUSIONS: Collectively, our data suggest that alpha7 nAChR plays a detrimental role in the host defense against C. neoformans- and HIV-1 associated comorbidity factors-induced BBB injury and CNS disorders. |
