Back to Search
Start Over
Alpha7 nicotinic acetylcholine receptor is required for blood-brain barrier injury-related CNS disorders caused by Cryptococcus neoformans and HIV-1 associated comorbidity factors.
- Source :
-
BMC Infectious Diseases . Aug2015, Vol. 15 Issue 1, p1-11. 11p. 2 Color Photographs, 1 Black and White Photograph, 3 Graphs. - Publication Year :
- 2015
-
Abstract
- 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 α7 nAChR is an essential regulator of inflammation, which contributes to regulation of NF-κB 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 α7 nAChR in host defense against CNS disorders caused by these comorbidities was demonstrated by chemical [inhibitor: methyllycaconitine (MLA)] and genetic (α7-/- mice) blockages of α7 nAChR. Results: As shown in our in vivo studies, BBB injury was significantly reduced in α7-/- mice infected with C. neoformans. Stimulation by the gp41 ectodomain peptide (gp41-I90) and METH was abolished in the α7-/- animals. C. neoformans and gp41-I90 could activate NF-κB. Gp41-I90- and METH-induced monocyte transmigration and senescence were significantly inhibited by MLA and CAPE (caffeic acid phenethyl ester, an NF-κB inhibitor). Conclusions: Collectively, our data suggest that α7 nAChR plays a detrimental role in the host defense against C. neoformans- and HIV-1 associated comorbidity factors-induced BBB injury and CNS disorders. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 14712334
- Volume :
- 15
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- BMC Infectious Diseases
- Publication Type :
- Academic Journal
- Accession number :
- 109228968
- Full Text :
- https://doi.org/10.1186/s12879-015-1075-9