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

Details

• Personal Author:
  Ahmed C ; Barnes MA ; Beezhold, Donald H. ; Block ML ; Croston TL ; Green, Brett J. ; Greve HJ ; Johnson JA Jr. ; Ladd TB ; Lemons, Angela R. ; Mumaw CL ; Simpson E ; Xuei X
• Description:
  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 × 10^5 spores), or viable A. versicolor (3 × 10^5 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. [Description provided by NIOSH]
• Subjects:
  Fungi Immune System Occupational Health Safety
• Keywords:
  Aspergillus Infection Author Keywords: Aspergillus Versicolor Brain Function Central Nervous System Filamentous Fungi Fungal Infections Gene Expression Immune Reaction Indoor Environments Microglia Neuroimmune Homeostasis Neuroinflammation Neurological Reactions Neuropeptides Neurotransmitters RNA-seq

  More +
• ISSN:
  1759-0914
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Indiana ; OSHA Region 3 ; OSHA Region 5 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  1-20
• Volume:
  13
• NIOSHTIC Number:
  nn:20064395
• Citation:
  ASN Neuro 2021 Jan-Dec; 13:1-20
• Contact Point Address:
  Michelle L. Block, Department of Pharmacology and Toxicology, Indiana University School of Medicine, The Stark Neurosciences Research Institute, Indianapolis, IN 46202, United States
• Email:
  mlblock@iupui.edu
• Federal Fiscal Year:
  2021
• Peer Reviewed:
  True
• Source Full Name:
  ASN Neuro
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:24f7c2c0389168b3fcc8296222d05f06ceabf532b29d6a58113873ac9a9cfcbbc377b8f73a9ee0e590aaaeb1743500f0c54ed6f8ab6f90707dafb46d2c12bc35
• Download URL:
  https://stacks.cdc.gov/view/cdc/222860/cdc_222860_DS1.pdf
• File Type:
  [PDF - 2.25 MB ]