Aspergillus versicolor Inhalation Triggers Neuroimmune, Glial, and Neuropeptide Transcriptional Changes

dc.contributor.authorLadd, Thatcher B.
dc.contributor.authorJohnson, James A., Jr.
dc.contributor.authorMumaw, Christen L.
dc.contributor.authorGreve, Hendrik J.
dc.contributor.authorXuei, Xiaoling
dc.contributor.authorSimpson, Ed
dc.contributor.authorBarnes, Mark A.
dc.contributor.authorGreen, Brett J.
dc.contributor.authorCroston, Tara L.
dc.contributor.authorAhmed, Chandrama
dc.contributor.authorLemons, Angela
dc.contributor.authorBeezhold, Donald H.
dc.contributor.authorBlock, Michelle L.
dc.contributor.departmentMedical and Molecular Genetics, School of Medicineen_US
dc.date.accessioned2022-11-21T12:22:48Z
dc.date.available2022-11-21T12:22:48Z
dc.date.issued2021
dc.description.abstractIncreasing 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.en_US
dc.eprint.versionFinal published versionen_US
dc.identifier.citationLadd TB, Johnson JA Jr, Mumaw CL, et al. Aspergillus versicolor Inhalation Triggers Neuroimmune, Glial, and Neuropeptide Transcriptional Changes. ASN Neuro. 2021;13:17590914211019886. doi:10.1177/17590914211019886en_US
dc.identifier.urihttps://hdl.handle.net/1805/30583
dc.language.isoen_USen_US
dc.publisherSageen_US
dc.relation.isversionof10.1177/17590914211019886en_US
dc.relation.journalASN Neuroen_US
dc.rightsAttribution-NonCommercial 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/*
dc.sourcePMCen_US
dc.subjectAspergillus versicoloren_US
dc.subjectRNA-seqen_US
dc.subjectFilamentous fungien_US
dc.subjectMicrogliaen_US
dc.subjectNeuroimmune homeostasisen_US
dc.subjectNeuropeptidesen_US
dc.subjectNeuroinflammationen_US
dc.titleAspergillus versicolor Inhalation Triggers Neuroimmune, Glial, and Neuropeptide Transcriptional Changesen_US
dc.typeArticleen_US
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