High-fat diet induced spatial working memory deficits in aged male rats and potential synaptic degradation in prefrontal cortex
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Date
2024-05
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The Ohio State University
Abstract
Alzheimer’s disease (AD) and other dementias are marked by debilitating cognitive challenges that affect many individuals in the aging population. Considering this population is projected to rapidly increase over the next few decades, it is extremely important to identify the factors that may contribute to the onset or exacerbation of these devasting conditions. Modifiable lifestyle habits, such as diet, have been shown to increase disease risk. Specifically, it is known that a high-fat diet (HFD) causes systemic inflammation and neuroinflammation. Neuroinflammation is an adaptive and protective response of the brain which helps preserve proper function of the central nervous system (CNS) in the face of pathogens or other danger signals, but exaggerated neuroinflammation is believed to be a key mechanism driving neurodegeneration. Our previous work has shown that short-term consumption of HFD can lead to exaggerated neuroinflammation and diminished cognitive functioning in aged rats. Specifically, HFD-fed aged rats exhibited deficits in contextual and cued fear memory compared to control rats. These impairments were found to be caused by exaggerated neuroinflammation in the hippocampus and amygdala, the brain regions known to mediate these types of memories. In the present study we examined the extent to which short-term HFD might impair working memory and evoke neuroinflammation or other synaptic-related deficits in the prefrontal cortex (PFC). We hypothesized that working memory would be impaired, that neuroinflammation would be exaggerated, and that synaptic elements would be diminished with HFD consumption. The data from this project indicate that working memory is indeed impaired in HFD-fed rats. Additionally, there are alterations in synaptic elements as a function of age. Interestingly, we did not observe an exaggerated neuroinflammatory response in the PFC at this time point. These findings suggest that HFD may affect various regions of the brain through differing pathways and with varying time courses.
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Keywords
high fat diet, spatial working memory, prefrontal cortex, aged male rats