Aspergillus versicolor Inhalation Dysregulates Neuroimmune Homeostasis and Augments Alzheimer’s Disease-Like Neuropathology

Details

• Personal Author:
  Barnes MA ; Beezhold, Donald H. ; Block ML ; Croston TL ; Dunbar AL ; Green, Brett J. ; Greve HJ ; Johnson JA Jr. ; Ladd TB ; 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 potential impact on CNS disease, particularly Alzheimer's disease (AD), is poorly understood. To characterize how Aspergillus versicolor, a common opportunistic filamentous fungi species associated with damp environments modifies the CNS transcriptional phenotype, 8-week-old female B6C3F1/N mice were exposed to filtered air, heat-inactivated A. versicolor (3 x 105 spores), or viable A. versicolor (3 x 105 spores) via nose-only inhalation twice a week for 4 weeks. Bulk RNA-seq analysis of the midbrain, the brain region determined to have the largest TNFá neuroinflammation response by RT-qPCR, revealed that 4 weeks of viable A. versicolor exposure resulted in significant transcriptional enrichment of neuroinflammation, glial cell activation, postsynaptic, and neurotransmission pathways. To discern the effect of A. versicolor on neurodegenerative disease processes, 8-week-old male 5xFAD mice were exposed to either filtered air or live A. versicolor (3X105 spores) twice a week for 13 weeks. Immunohistochemical analysis of AD-like neuropathology in the cortex demonstrated an increase in the number of Thioflavin S+ plaques in the cortex with A. versicolor exposure, supporting that inhalation of viable filamentous fungi can augment amyloid plaque pathology in the 5xFAD AD mouse model. Analysis of the circulating factors revealed that serum IL-5 and CXCL10 were elevated in both 5xFAD and control mice, both serum IL-12 and IL-10 decreased in only 5xFAD mice, and HMGB1 was elevated in only 5xFAD mice in response to A. versicolor exposure. Together, these findings indicate A. versicolor inhalation can dysregulate neuroimmune homeostasis, uniquely modify circulating factors in 5xFAD mice, and augment ongoing AD-like neuropathology, providing much needed insight into how inhaled fungal exposures may affect CNS disease. [Description provided by NIOSH]
• Subjects:
  Animals Fungi Laboratories Nervous System Nervous System Diseases Occupational Health Safety Toxicology
• Keywords:
  Brain Function Central Nervous System Cognitive Function Emotional Stress Indoor Environments Laboratory Animals Neurological Disorders Psychological Disorders
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• 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
• Volume:
  180
• NIOSHTIC Number:
  nn:20062276
• Citation:
  Toxicologist 2021 Mar; 180(S1):231
• Federal Fiscal Year:
  2021
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 60th Annual Meeting and ToxExpo, March 12-26, 2021, Virtual Event
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:7b1719312a09fd0c4bc49989ae069adead01469607f3ab0f2b78e4fe96ec9c990fa5beb2489431bf7bced6b218d9ca2ce4d3216dfa79d1a86852f8d8cfc9039e
• Download URL:
  https://stacks.cdc.gov/view/cdc/225556/cdc_225556_DS1.pdf
• File Type:
  [PDF - 147.16 KB ]