Role of Alpha7 Nicotinic Receptor in Meningitis Pathogenesis
Author Information
Author(s): Chi Feng, Wang Lin, Zheng Xueye, Wu Chun-Hua, Jong Ambrose, Sheard Michael A., Shi Wei, Huang Sheng-He
Primary Institution: Department of Pediatrics, Saban Research Institute, University of Southern California, Childrens Hospital Los Angeles, Los Angeles, California, United States of America
Hypothesis
Does the alpha7 nicotinic acetylcholine receptor (nAChR) contribute to the regulation of bacterial meningitis?
Conclusion
The alpha7 nAChR plays a detrimental role in host defense against meningitic infection by modulating pathogen invasion and inflammatory responses.
Supporting Evidence
- α7 nAChR deficiency reduced E. coli invasion and PMN transmigration across the blood-brain barrier.
- Nicotine enhanced E. coli K1 invasion in a dose-dependent manner.
- Proinflammatory cytokines were significantly reduced in the cerebrospinal fluids of α7-/- mice with E. coli meningitis.
- α7 nAChR is the major calcium channel for nicotine- and E. coli K1-induced intracellular calcium concentrations.
- α7 nAChR blockade reduced neuronal injury in the hippocampus during meningitis.
- Tobacco smoke exposure increased susceptibility to E. coli meningitis in neonatal mice.
- α7 nAChR-mediated calcium signaling is crucial for the inflammatory response to bacterial infection.
- Blocking α7 nAChR improved outcomes in models of bacterial meningitis.
Takeaway
This study found that a specific receptor in the brain, called alpha7 nAChR, makes it easier for bacteria to invade and cause meningitis, especially when nicotine is present.
Methodology
The study used both in vitro and in vivo models, including α7-deficient mouse brain microvascular endothelial cells and animal models, to assess the role of alpha7 nAChR in bacterial invasion and inflammation.
Potential Biases
Potential bias in the interpretation of results due to the specific focus on alpha7 nAChR without considering other pathways.
Limitations
The study primarily focused on neonatal mice, which may not fully represent adult responses.
Participant Demographics
Neonatal mice were used in the study.
Statistical Information
P-Value
p<0.01
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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