Intermittent Systemic Exposure to Lipopolysaccharide-Induced Inflammation Disrupts Hippocampal Long-Term Potentiation and Impairs Cognition in Aging Male Mice

Details

• Personal Author:
  Billig, B. K. ; Engler-Chiurazzi, E. B. ; Felton, C. C. ; Hammock, J. ; McDonald, K. O. ; O'Callaghan, J. P. ; Porter, K. N. ; Povroznik, J. M. ; Russell, A. E. ; Schreurs, B. G. ; Simpkins, J. W. ; Wang, D. S. ; Yilmaz, A. ; Zwezdaryk, K. J.
• Description:
  Age-related cognitive decline, a common component of the brain aging process, is associated with significant impairment in daily functioning and quality of life among geriatric adults. While the complexity of mechanisms underlying cognitive aging are still being elucidated, microbial exposure and the multifactorial inflammatory cascades associated with systemic infections are emerging as potential drivers of neurological senescence. The negative cognitive and neurobiological consequences of a single pathogen-associated inflammatory experience, such as that modeled through treatment with lipopolysaccharide (LPS), are well documented. Yet, the brain aging impacts of repeated, intermittent inflammatory challenges are less well studied. To extend the emerging literature assessing the impact of infection burden on cognitive function among normally aging mice, here, we repeatedly exposed adult mice to intermittent LPS challenges during the aging period. Male 10-month-old C57BL6 mice were systemically administered escalating doses of LPS once every two weeks for 2.5 months. We evaluated cognitive consequences using the non-spatial step-through inhibitory avoidance task, and both spatial working and reference memory versions of the Morris water maze. We also probed several potential mechanisms, including cortical and hippocampal cytokine/chemokine gene expression, as well as hippocampal neuronal function via extracellular field potential recordings. Though there was limited evidence for an ongoing inflammatory state in cortex and hippocampus, we observed impaired learning and memory and a disruption of hippocampal long-term potentiation. These data suggest that a history of intermittent exposure to LPS-induced inflammation is associated with subtle but significantly impaired cognition among normally aging mice. The broader impact of these findings may have important implications for standard of care involving infections in aging individuals or populations at-risk for dementia. [Description provided by NIOSH]
• Subjects:
  Aging Animals Communicable Diseases Immune System Lipids Microbiology Nervous System Occupational Health Safety
• Keywords:
  Animal Studies Author Keywords: Brain Aging Brain Function Cognitive Aging Cognitive Function Hippocampus Immune System Infection Burden Infectious Diseases Learning And Memory Lipopolysaccharide Long-term Potentiation Neuroinflammation Neurological System Pathogens Synaptic Plasticity Systemic Inflammation

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• ISSN:
  0889-1591
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Louisiana ; OSHA Region 3 ; OSHA Region 6 ; Pennsylvania ; 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:
  13 pdf pages
• Volume:
  108
• NIOSHTIC Number:
  nn:20066659
• Citation:
  Brain Behav Immun 2023 Feb; 108:279-291
• Contact Point Address:
  E.B. Engler-Chiurazzi, Department of Neuroscience, Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV 26505, USA
• Email:
  eenglerchiurazzi@tulane.edu
• Federal Fiscal Year:
  2023
• Peer Reviewed:
  True
• Source Full Name:
  Brain, Behavior, and Immunity
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:a61ad43e9e083c0350ea93d85f873c1cdd3981164905a19ea6679011a616dcc6d2ad011db92209e7b3c65d531cb4fdea6c98001738c5ddfeb24b7356ee6eeffc
• Download URL:
  https://stacks.cdc.gov/view/cdc/230761/cdc_230761_DS1.pdf
• File Type:
  [PDF - 2.20 MB ]