Moderate Aspergillus versicolor Inhalation Exposure Triggers Neuroinflammation

Details

• Personal Author:
  Barnes MA ; Beezhold, Donald H. ; Block ML ; Green, Brett J. ; Ladd TB ; Mumaw CL
• Description:
  Increasing evidence implicates indoor mold exposure in cognitive deficits in children, a process hypothesized to also occur in adults. However, the mechanisms by which inhaled mold and the associated allergic pulmonary response might impact the brain are unknown. Though neuroinflammation is associated with memory deficits and impaired cognition, the environmental triggers of neuroinflammation are poorly understood and the central nervous system (CNS) pro-inflammatory consequences of inhaling mold spores is largely unknown. To address whether a moderate exposure to a common mold found in damp indoor environments, Aspergillus versicolor (AV), could cause neuroinflammation, 8 week old female B6C3F1/N mice were exposed to filtered air, 1x10(5) heat inactivated AV spores, or 1x10(5) live AV spores 2 times per week for 1, 2, or 4 weeks. At 48 H after the final exposure, the neuroinflammation marker profile was assessed by RT-qPCR. Analysis of brain tissue from the 4 week exposure revealed significantly elevated pro-inflammatory markers in response to only the live AV exposure in several brain regions: the olfactory bulb (TNFalpha), frontal lobe (TNFalpha, IL-1beta, and CX3CR1), midbrain, and cerebellum (TNFalpha and CX3CR1). To discern how early neuroinflammation began in response to AV inhalation, 1 and 2 week exposure samples were tested for TNFalpha mRNA expression. Interestingly, results demonstrate that heat inactivated AV significantly increased TNFalpha mRNA levels in the olfactory bulb in the 1 week exposure, but not in the 2 or 4 week exposures. In response to inhalation of live AV, TNFalpha mRNA levels were significantly elevated in brain tissue from 1 week exposure (olfactory bulb and midbrain) and 2 week exposure (frontal lobe, midbrain, and cerebellum). Taken together, these results demonstrate that inhalation of live AV spores triggers neuroinflammation in several brain regions with 1, 2, and 4 week exposures, suggesting a generalized CNS response. However, heat inactivated spores were shown to exert a CNS pro-inflammatory response in only the initial, early 1 week exposure. These findings provide much needed insight into the underlying mechanisms of how the allergic pulmonary response and mold inhalation exposure affects the brain. [Description provided by NIOSH]
• Subjects:
  Environmental Exposure Fungi Hypersensitivity Immune System Laboratories Microbiology Nervous System Occupational Health Respiratory System Safety Toxicology

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• Keywords:
  Allergic Reactions Aspergillus Infection Biological Effects Brain Function Brain Matter Cell Signaling Central Nervous System Cognitive Function Cytokines Dose Response Exposure Assessment Exposure Levels Immune Reaction Indoor Environments Inhalation Laboratory Animals Laboratory Testing Microorganisms Molds Neurological Reactions Neurological System Proteins

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Indiana ; Maryland ; 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:
  246-247
• Volume:
  168
• Issue:
  1
• NIOSHTIC Number:
  nn:20054962
• Citation:
  Toxicologist 2019 Mar; 168(1):246-247
• Federal Fiscal Year:
  2019
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 58th Annual Meeting and ToxExpo, March 10-14, 2019, Baltimore, Maryland
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:0f0e6818ced018c0f8bbf9af9d9e6891878f1f6b9f536aae8939b9f1ff253a1db3cafe59bb4943847ce008220ae4e1cdb46fb798874f3c3f56996c591f3cd7be
• Download URL:
  https://stacks.cdc.gov/view/cdc/217368/cdc_217368_DS1.pdf
• File Type:
  [PDF - 915.45 KB ]