Summary: Frequent bouts of common infections such as colds or the flu may accelerate brain aging, contribute to cognitive decline, and raise the risk of dementia. In a study of aging male mice, repeated episodes of moderate inflammation produced measurable memory deficits and disrupted neuronal signaling.
Source: Tulane University
Frequent illness may influence the pace of brain aging and increase the likelihood of dementia or other cognitive disorders.
Researchers at Tulane University, in collaboration with West Virginia University and the National Institute for Occupational Safety and Health, report evidence that recurrent, intermittent inflammatory events can impair cognition and alter neuronal communication. Their findings were published in the journal Brain, Behavior and Immunity.
The team studied adult male mice approaching middle age and exposed them to repeated, moderate inflammatory challenges intended to model common, intermittent infections such as seasonal influenza or colds. After a relatively small number of these inflammatory episodes, the mice showed declines in learning and memory alongside disruptions in hippocampal function.
“We wanted to know whether variation in infection history could help explain some of the differences we observe in dementia rates across the population,” said lead author Elizabeth Engler-Chiurazzi, PhD, a behavioral neuroscientist in the Tulane Department of Neurosurgery. “These animals began the study with normal function, but following intermittent inflammatory exposure they remembered less and their neurons performed more poorly.”
This is the first study to intentionally model repeated, intermittent inflammatory exposures in mice and to examine their long-term impact on brain health. Laboratory mice typically encounter far fewer infections than humans do over a lifetime; thus, the cognitive effects seen after only a handful of inflammatory episodes in mice suggest the potential for stronger or more persistent effects in people.
“We only exposed the mice to sickness-like inflammation a few times, so finding any impairment at all was unexpected,” Engler-Chiurazzi added. “The changes were subtle, but those subtle changes can accumulate. In humans, similar episodes might not be obvious day to day yet could contribute to accelerated cognitive aging over time.”
The study’s results carry potential implications for clinical care and infection prevention in older adults and populations at risk for dementia. The findings are particularly relevant amid ongoing attention to COVID-19 and long-COVID, since inflammation triggered by infection is a mechanistic link under investigation for long-term neurological consequences.
Engler-Chiurazzi emphasized the need for further research to clarify the biological pathways that connect intermittent infections to brain aging, and to identify strategies that could prevent or reduce these effects. She also noted the importance of studying whether groups facing health disparities might experience a greater cumulative neurological burden from repeated infections.
“A practical takeaway from this work is the importance of staying as healthy and infection-free as possible, especially for people at risk of cognitive decline,” she said.
About this Alzheimer’s disease research news
Author: Andrew Yawn
Source: Tulane University
Contact: Andrew Yawn – Tulane University
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Original Research: Open access. “Intermittent systemic exposure to lipopolysaccharide-induced inflammation disrupts hippocampal long-term potentiation and impairs cognition in aging male mice” by Elizabeth Engler-Chiurazzi et al., Brain, Behavior, and Immunity. DOI: 10.1016/j.bbi.2022.12.013
Abstract
Intermittent systemic exposure to lipopolysaccharide-induced inflammation disrupts hippocampal long-term potentiation and impairs cognition in aging male mice
Age-related cognitive decline is a common element of brain aging and can majorly affect daily functioning and quality of life in older adults. While multiple mechanisms contribute to cognitive aging, repeated microbial exposure and the inflammatory processes triggered by systemic infections have emerged as possible contributors to accelerated neurological aging.
Previous research has documented the harmful cognitive and neurobiological effects of a single immune-activating event modeled by lipopolysaccharide (LPS). However, the long-term brain effects of repeated, intermittent inflammatory insults are less well characterized. To address this gap, the investigators exposed adult male mice to escalating doses of LPS every two weeks for 2.5 months, beginning at 10 months of age—an age corresponding to mature adulthood in mice.
Cognitive performance was assessed using non-spatial inhibitory avoidance and both working and reference memory versions of the Morris water maze. In addition, the researchers examined potential mechanisms by measuring cytokine and chemokine gene expression in cortex and hippocampus and assessing hippocampal neuronal function with extracellular field potential recordings.
Although measures showed limited evidence of a persistent inflammatory state in cortex and hippocampus, the mice displayed impaired learning and memory and a disruption of hippocampal long-term potentiation—a key physiological substrate of memory. These results indicate that a history of intermittent, LPS-induced inflammation can produce subtle but significant cognitive deficits in normally aging mice.
The broader implications of these findings suggest that infection management and preventative care for older individuals or those at higher risk of dementia may need reevaluation, given the potential for repeated inflammatory events to contribute to cognitive decline and altered brain function.