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慢性尼古丁暴露小鼠遗传模型中的年龄相关性牙齿缺失和口腔微生物失调。

Age-Associated Tooth Loss and Oral Microbial Dysbiosis in a Mouse Genetic Model of Chronic Nicotine Exposure.

机构信息

Salt Lake City Veterans Affairs Medical Center: Geriatrics, Research, Education and Clinical Center, Salt Lake City, UT, United States.

Department of Neurobiology, University of Utah School of Medicine, Salt Lake City, UT, United States.

出版信息

Front Immunol. 2020 Oct 7;11:575200. doi: 10.3389/fimmu.2020.575200. eCollection 2020.

Abstract

Nicotine acts as a potent modulator of normal cellular responses through the nicotinic acetylcholine receptor subtype alpha7. In a mouse genetic model of alpha7 receptor dysfunction, alpha7, 85 percent of 18 month-old mice exhibit an age-associated spontaneous loosening or complete loss of 3rd molars that was not present in the control mice. The adjacent soft tissues appeared largely unaffected. Further analysis including micro-CT revealed evidence of bone loss surrounding the 3rd molars with areas of cavitation and/or sponge-like (cancellous) bone remodeling in the mandible. The mandible microbiome was examined using 16S-rRNA sequencing. The results show the alpha7 oral microbiome included increased landscape complexity indicative of dysbiosis, and a significant increase of some bacteria, particularly . These results suggest that normal alpha7 function plays a relevant role in maintaining normal gene expression and oral microbiome stasis. Consequently, this mouse model suggests there are consequences to ongoing alpha7 receptor dysfunction and oral health, as can occur from chronic exposure to nicotine as expected from electronic nicotine delivery systems (ENDS or "vaping"), that may not be seen until older age.

摘要

尼古丁通过烟碱型乙酰胆碱受体亚型 alpha7 作为一种有效的调节剂,作用于正常的细胞反应。在 alpha7 受体功能障碍的小鼠遗传模型中,85%的 18 月龄小鼠出现与年龄相关的自发性第三磨牙松动或完全缺失,而对照组小鼠则没有这种情况。相邻的软组织似乎基本不受影响。进一步的分析,包括微 CT 显示,第三磨牙周围有骨丢失的证据,下颌骨有囊腔和/或海绵样(松质)骨重塑的区域。使用 16S-rRNA 测序检查下颌骨微生物组。结果表明,alpha7 口腔微生物组包括增加的复杂性,表明存在生态失调,以及某些细菌的显著增加,特别是 。这些结果表明,正常的 alpha7 功能在维持正常的基因表达和口腔微生物组稳定方面发挥着相关作用。因此,这种小鼠模型表明,持续的 alpha7 受体功能障碍和口腔健康会产生后果,正如从电子尼古丁输送系统(ENDS 或“电子烟”)的慢性暴露中所预期的那样,这种后果可能要到老年才会显现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5a7/7575759/9196e291610b/fimmu-11-575200-g0001.jpg

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