Aspergillus versicolor Inhalation Triggers Neuroimmune, Glial, and Neuropeptide Transcriptional Changes.
Aspergillus versicolor Inhalation Triggers Neuroimmune, Glial, and Neuropeptide Transcriptional Changes.
复制标题
DOI：
10.1177/17590914211019886
复制
发表时间：
2021-01
期刊：
影响因子：
4.7
通讯作者：
Block ML
中科院分区：
文献类型：
--
作者：
Ladd TB;Johnson JA Jr;Mumaw CL;Greve HJ;Xuei X;Simpson E;Barnes MA;Green BJ;Croston TL;Ahmed C;Lemons A;Beezhold DH;Block ML
越来越多的证据表明，室内真菌暴露与有害的中枢神经系统（CNS）健康有关，例如儿童和成人的认知和情感缺陷，但其可能影响大脑的具体机制尚不清楚。将小鼠暴露于过滤空气、热灭活的杂色曲霉（3 × 105个孢子）或活的A.通过仅鼻吸入暴露，每周2次，持续1周、2周或4周，对变色菌（3 × 105个孢子）进行接种。对暴露于活性A的小鼠的皮质、中脑、嗅球和小脑组织的分析。与过滤空气对照组相比，1、2和4周的变色孢子暴露显示，在几个脑区域中，促炎性（Tnf和Il 1b）和神经胶质活性（GDNF和Cxc 3r 1）基因表达显著升高，在暴露4周后48小时，中脑和额叶中的神经免疫应答最一致和最明显。中脑组织的大量RNA-seq分析证实，A.与过滤空气对照相比，变色暴露导致几种生物途径的显著转录富集，包括神经炎症、神经胶质细胞活化和突触后组织的调节。在4周A. versicolor暴露了中脑组织，强调了对神经传递重要的基因表达受到重复A.变色吸入暴露。综上所述，这些发现表明，大脑可以检测到A。因此，本研究旨在探讨真菌吸入暴露对神经免疫和神经传递基因表达的影响，为了解吸入性真菌暴露如何影响中枢神经系统反应和调节神经免疫稳态提供急需的见解。
Increasing evidence associates indoor fungal exposure with deleterious central nervous system (CNS) health, such as cognitive and emotional deficits in children and adults, but the specific mechanisms by which it might impact the brain are poorly understood. Mice were exposed to filtered air, heat-inactivated Aspergillus versicolor (3 × 105 spores), or viable A. versicolor (3 × 105 spores) via nose-only inhalation exposure 2 times per week for 1, 2, or 4 weeks. Analysis of cortex, midbrain, olfactory bulb, and cerebellum tissue from mice exposed to viable A. versicolor spores for 1, 2, and 4 weeks revealed significantly elevated pro-inflammatory (Tnf and Il1b) and glial activity (Gdnf and Cxc3r1) gene expression in several brain regions when compared to filtered air control, with the most consistent and pronounced neuroimmune response 48H following the 4-week exposure in the midbrain and frontal lobe. Bulk RNA-seq analysis of the midbrain tissue confirmed that 4 weeks of A. versicolor exposure resulted in significant transcriptional enrichment of several biological pathways compared to the filtered air control, including neuroinflammation, glial cell activation, and regulation of postsynaptic organization. Upregulation of Drd1, Penk, and Pdyn mRNA expression was confirmed in the 4-week A. versicolor exposed midbrain tissue, highlighting that gene expression important for neurotransmission was affected by repeated A. versicolor inhalation exposure. Taken together, these findings indicate that the brain can detect and respond to A. versicolor inhalation exposure with changes in neuroimmune and neurotransmission gene expression, providing much needed insight into how inhaled fungal exposures can affect CNS responses and regulate neuroimmune homeostasis.
登录
查看更多内容
影响因子：
3.8
作者：
Klocke, Carolyn;Allen, Joshua L.;Cory-Slechta, Deborah A.
通讯作者：
Cory-Slechta, Deborah A.
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
DOI：
10.1073/pnas.1318830110
发表时间：
2013-11-26
影响因子：
11.1
作者：
Inamdar, Arati A.;Hossain, Muhammad M.;Bennett, Joan Wennstrom
通讯作者：
Bennett, Joan Wennstrom
影响因子：
3.5
作者：
Hyvonen, Saija;Lohi, Jouni;Tuuminen, Tamara
通讯作者：
Tuuminen, Tamara
影响因子：
4.2
作者：
Hutson, Che Brown;Lazo, Carlos R.;Chesselet, Marie-Francoise
通讯作者：
Chesselet, Marie-Francoise