Abstract

Background:

Chronic environmental exposure to manganese (Mn) can cause debilitating damage to the central nervous system. However, its potential toxic effects on the enteric nervous system (ENS) have yet to be assessed.

Objective:

We examined the effect of Mn on the ENS using both cell and animal models.

Method:

Rat enteric glial cells (EGCs) and mouse primary enteric cultures were exposed to increasing concentrations of Mn and cell viability and mitochondrial health were assessed using various morphological and functional assays. C57BL/6 mice were exposed daily to a sublethal dose of Mn ($15\mathrm{mg}/\mathrm{kg}/\mathrm{d}$) for 30 d. Gut peristalsis, enteric inflammation, gut microbiome profile, and fecal metabolite composition were assessed at the end of exposure.

Results:

EGC mitochondria were highly susceptible to Mn neurotoxicity, as evidenced by lower mitochondrial mass, adenosine triphosphate–linked respiration, and aconitase activity as well as higher mitochondrial superoxide, upon Mn exposure. Minor differences were seen in the mouse model: specifically, longer intestinal transit times and higher levels of colonic inflammation.

Conclusion:

Based on our findings from this study, Mn preferentially induced mitochondrial dysfunction in a rat EGC line and in vivo resulted in inflammation in the ENS. https://doi.org/10.1289/EHP7877

中文翻译：

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慢性锰暴露与肠神经系统：一项体外和小鼠体内研究

摘要

背景：

长期接触锰 (Mn) 环境会对中枢神经系统造成严重损害。然而，其对肠神经系统 (ENS) 的潜在毒性作用尚未得到评估。

客观的：

我们使用细胞和动物模型检查了 Mn 对 ENS 的影响。

方法：

大鼠肠神经胶质细胞 (EGC) 和小鼠原代肠道培养物暴露于浓度不断增加的 Mn，并使用各种形态学和功能测定法评估细胞活力和线粒体健康。C57BL/6 小鼠每天暴露于亚致死剂量的 Mn（$15\mathrm{毫克}/\mathrm{公斤}/\mathrm{d}$) 30 天。在暴露结束时评估肠道蠕动、肠道炎症、肠道微生物组特征和粪便代谢物组成。

结果：

EGC 线粒体对锰神经毒性非常敏感，这可以通过较低的线粒体质量、三磷酸腺苷相关的呼吸作用和乌头酸酶活性以及较高的线粒体超氧化物来证明，在锰暴露下。在小鼠模型中观察到微小差异：具体而言，肠道转运时间更长，结肠炎症水平更高。

结论：

根据我们在这项研究中的发现，Mn 优先诱导大鼠 EGC 系中的线粒体功能障碍，并在体内导致 ENS 中的炎症。https://doi.org/10.1289/EHP7877