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.

越来越多的证据将室内真菌暴露与有害的中枢神经系统 (CNS) 健康联系起来，例如儿童和成人的认知和情绪缺陷，但人们对它可能影响大脑的具体机制知之甚少。每周 2 次仅通过鼻子吸入，将小鼠暴露于过滤空气、热灭活的Aspergillus versicolo r（3 × 10 ⁵孢子）或活的A. versicolo r（3 × 10 ⁵孢子），持续 1、2 或4周。对暴露于活的云芝孢子 1、2 和 4 周的小鼠的皮质、中脑、嗅球和小脑组织进行分析，结果显示促炎（ Tnf 和 Il1b）和神经胶质活性显着升高。与过滤空气对照相比， Gdnf和Cxc3r1 ) 在几个大脑区域的基因表达，在中脑和额叶暴露 4 周后，48 小时神经免疫反应最一致和最明显。对中脑组织的批量 RNA-seq 分析证实，与过滤空气对照相比，4 周的A. versicolo暴露导致几种生物途径的显着转录富集，包括神经炎症、神经胶质细胞活化和突触后组织的调节。Drd1、Penk和Pdyn mRNA 表达的上调在 4 周的A. versicolo中得到证实r 暴露中脑组织，强调对神经传递重要的基因表达受到重复的杂色曲霉吸入暴露的影响。综上所述，这些发现表明，大脑可以检测并响应A. versicolo吸入暴露与神经免疫和神经传递基因表达的变化，从而提供急需的洞察力来了解吸入真菌暴露如何影响 CNS 反应和调节神经免疫稳态。