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Mold inhalation causes innate immune activation, neural, cognitive and emotional dysfunction
Brain, Behavior, and Immunity ( IF 15.1 ) Pub Date : 2020-07-01 , DOI: 10.1016/j.bbi.2019.11.006
Cheryl F Harding 1 , Carolyn L Pytte 2 , Kimberly G Page 3 , Kelly J Ryberg 4 , Edna Normand 5 , Gregory J Remigio 4 , Richard A DeStefano 6 , David B Morris 7 , Julia Voronina 8 , Ariel Lopez 9 , Lauren A Stalbow 10 , Erin P Williams 10 , Nohely Abreu 9
Affiliation  

Individuals living or working in moldy buildings complain of a variety of health problems including pain, fatigue, increased anxiety, depression, and cognitive deficits. The ability of mold to cause such symptoms is controversial since no published research has examined the effects of controlled mold exposure on brain function or proposed a plausible mechanism of action. Patient symptoms following mold exposure are indistinguishable from those caused by innate immune activation following bacterial or viral exposure. We tested the hypothesis that repeated, quantified doses of both toxic and nontoxic mold stimuli would cause innate immune activation with concomitant neural effects and cognitive, emotional, and behavioral symptoms. We intranasally administered either 1) intact, toxic Stachybotrys spores; 2) extracted, nontoxic Stachybotrys spores; or 3) saline vehicle to mice. As predicted, intact spores increased interleukin-1β immunoreactivity in the hippocampus. Both spore types decreased neurogenesis and caused striking memory deficits in young mice, while decreasing pain thresholds and enhancing auditory-cued memory in older mice. Nontoxic spores also increased anxiety-like behavior. Levels of hippocampal immune activation correlated with decreased neurogenesis, contextual memory deficits, and/or enhanced auditory-cued fear memory. Innate-immune activation may explain how both toxic mold and nontoxic mold skeletal elements caused cognitive and emotional dysfunction.

中文翻译:

霉菌吸入导致先天免疫激活、神经、认知和情绪功能障碍

在发霉的建筑物中生活或工作的人会抱怨各种健康问题,包括疼痛、疲劳、焦虑、抑郁和认知缺陷。霉菌引起此类症状的能力是有争议的,因为没有已发表的研究检查过受控霉菌暴露对大脑功能的影响或提出了一种合理的作用机制。霉菌暴露后的患者症状与细菌或病毒暴露后先天免疫激活引起的症状无法区分。我们测试了以下假设,即重复、量化剂量的有毒和无毒霉菌刺激物会导致先天免疫激活,并伴随神经效应和认知、情绪和行为症状。我们鼻内施用 1) 完整、有毒的葡萄孢子;2) 提取的、无毒的葡萄孢子;或 3) 小鼠的生理盐水载体。正如预测的那样,完整的孢子增加了海马体中白细胞介素-1β 的免疫反应性。两种孢子类型都减少了年轻小鼠的神经发生并导致显着的记忆缺陷,同时降低了老年小鼠的疼痛阈值并增强了听觉提示记忆。无毒孢子也增加了类似焦虑的行为。海马体免疫激活水平与神经发生减少、情境记忆缺陷和/或增强的听觉恐惧记忆相关。先天免疫激活可以解释有毒霉菌和无毒霉菌骨骼元素如何导致认知和情绪功能障碍。同时降低疼痛阈值并增强老年小鼠的听觉记忆。无毒孢子也增加了类似焦虑的行为。海马体免疫激活水平与神经发生减少、情境记忆缺陷和/或增强的听觉恐惧记忆相关。先天免疫激活可以解释有毒霉菌和无毒霉菌骨骼元素如何导致认知和情绪功能障碍。同时降低疼痛阈值并增强老年小鼠的听觉记忆。无毒孢子也增加了类似焦虑的行为。海马体免疫激活水平与神经发生减少、情境记忆缺陷和/或增强的听觉恐惧记忆相关。先天免疫激活可以解释有毒霉菌和无毒霉菌骨骼元素如何导致认知和情绪功能障碍。
更新日期:2020-07-01
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