Medical advice for individuals with mild-to-moderate infections generally involves getting adequate rest and increasing fluid intake. Interestingly, a recent study published in the journal Brain, Behavior, and Immunity suggests that repeated inflammation caused by the administration of a bacterial toxin to middle-aged mice led to cognitive deficits.
These cognitive deficits were also accompanied by changes in the plasticity of neurons in the hippocampus, a region that plays a central role in learning and memory.
Elderly individuals are more susceptible to microbial infections, and such infections could worsen the decline in cognitive function in these individuals, leading to mild cognitive impairment or dementia.
A decline in certain cognitive abilities is observed over the course of normal aging and is a consequence of the biological processes associated with brain aging.
Studies in animal models have shown that inflammation due to microbial exposure can influence cognitive function. One of the models for examining the impact of inflammation caused by microbial infections involves injecting animals with the toxin lipopolysaccharide (LPS) that is present in the outer membrane of gram-negative bacteria.
These animal studies have shown that LPS administration can increase the levels of cytokines, a class of inflammatory proteins, in the brain and cause deficits in cognitive function. In addition, these adverse effects of LPS become more pronounced with advancing age.
To further understand the impact of lifetime exposure to microbial infections on cognitive function, the study’s authors assessed the impact of recurring inflammation caused by intermittent LPS injections on the cognitive function of healthy middle-aged mice.
The researchers used a progressively higher dose of LPS over the course of the five injections. Each injection of LPS resulted in moderate sickness, from which the mice recovered during the 15-day period.
The researchers then conducted behavioral tests to assess the cognitive function of the animals two weeks after the final lipopolysaccharide dose. The researchers also sacrificed the animals to examine the impact of lipopolysaccharide-induced inflammation on the brain at 5-6 weeks after the final injection.
The researchers found that mice receiving the LPS injections showed cognitive deficits in learning and retention of memory of information learned during the previous day.
After examining brain tissue, researchers saw that mice intermittently injected with LPS also showed changes in the hippocampus. The hippocampus plays a key role in memory and learning and is one of the regions that shows the earliest signs of degeneration in Alzheimer’s disease.
These changes included an increase in the expression of the gene for the cytokine interleukin-6 (IL-6) in the hippocampus of LPS-treated mice. This is consistent with previous studies showing elevated IL-6 levels in brain regions involved in cognition after LPS administration.
These results suggest that repeated LPS-induced inflammation in middle-aged mice can lead to cognitive deficits accompanied by changes in the hippocampus.
The study’s co-author Dr. Elizabeth Engler-Chiurazzi, a behavioral neuroscientist at Tulane University, said the findings have important implications for brain health and disease in humans.
“[O]ur findings may be the first step in a series of studies that could indicate that treatment for the common cold or other sources of intermittent infection among patients at high risk for cognitive decline/dementia may need to be more aggressive than the standard recommendations of rest and fluids”, said Dr. Elizabeth.
The findings of the present study suggest that more aggressive treatments could be necessary for older adults to prevent the lasting effects of these infections on cognitive function. However, it is important to note that this study was conducted in a mouse model, and the generalizability of these results to humans is not yet known.
E.B. Engler-Chiurazzi, A.E. Russell, J.M. Povroznik, K.O. McDonald, K.N. Porter, D.S. Wang, J. Hammock, B.K. Billig, C.C. Felton, A. Yilmaz, B.G. Schreurs, J.P. O’Callaghan, K.J. Zwezdaryk, J.W. Simpkins. Intermittent systemic exposure to lipopolysaccharide-induced inflammation disrupts hippocampal long-term potentiation and impairs cognition in aging male mice. Brain, Behavior, and Immunity. Volume 108. 2023. Pages 279-291, ISSN 0889-1591, https://doi.org/10.1016/j.bbi.2022.12.013.
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