Research into neuroprotective strategies aimed at correcting diet- and aging-related hippocampal dysfunction is of high relevance given the increasing prevalence of the Western diet and global population aging. This study investigated the effects of a long-term high-fat diet (HFD) and the antioxidant astaxanthin (AST) on the hippocampal state during aging in mice. Aging was shown to be accompanied by the impairment of long-term memory and the development of chronic neuroinflammation in the hippocampus. HFD had a moderate effect on hippocampal alterations compared to animals fed a standard diet (SD). The age-related dynamics of microglial activity, assessed by Iba1 immunoreactivity, was characterized by its increase in the hippocampal CA1 and CA3 regions and dentate gyrus (DG) at 12 months, followed by a decrease at 15 months. Dietary AST supplementation led to improved passive avoidance performance and exerted a duration-dependent effect: when administered for less than 6 months, AST promoted the suppression of pro-inflammatory activity, as evidenced by the downregulation of NF-κB expression in the hippocampus. However, longer continuous AST administration, conversely, led to the upregulation of NF-κB expression. These results indicate the ambiguous effects of HFD on the brain and emphasize the importance of optimizing the timing of antioxidant administration for protecting the hippocampus from neuroinflammation.
Fedorova et al. (Sun,) studied this question.