(P27-032-23) Modeling Effects of Dietary Compounds on Cognitive Aging

Objectives: Non-pathological aging is characterized by loss of synapses, the cellular structures that connect neurons, alterations in connectivity, and changes in neuroinflammation. These age-dependent changes are highly variable in severity. Notably, the extent of synaptic loss is correlated with the extent of memory impairment. More severe synapse loss occurs in age-related neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease. Of particular relevance to cognitive aging are the hippocampus and frontal cortex, brain regions involved in declarative memory, working memory, and executive functions. Nutritional interventions are emerging as a preventative and therapeutic mechanism to delay age-related cognitive decline. Specifically, diets high in polyunsaturated fatty acids, polyphenols, and flavonoids have been related to decreased risk of developing Alzheimer’s disease. These micronutrients may be involved with the maintenance of synaptic connectivity and reducing inflammation on a transcriptional level.

Methods: Our approach uses organotypic slice cultures of mouse cortex and hippocampus treated with micronutrients as an ex vivo model, followed by testing the effects of dietary compounds in vivo in mouse models of neurodegeneration. Synapse number, aging and cellular senescence relevant pathways, neuroinflammation, and oxidative stress will be measured by immunohistochemistry. Mesoscale imaging of synapses is being correlated with studies of cognitive impairment assessed through behavioral tasks. These approaches combine medium-throughput ex vivo and disease-relevant in vivo approaches.

Results: The carbocyclic sugar alcohol myo-inositol has been shown by our group to robustly increase synaptic density in vivo during brain development and in aging hippocampal slice cultures. Further, our studies in human neurons have demonstrated that the omega-3 fatty acid docosahexaenoic acid (DHA) increases synapse density and size, indicating stronger synapses.

Conclusions: This work expands our understanding of the relationship between diet and age-related decline in neuronal connectivity and cognition. With an increasing focus on precision nutrition, this work can help inform aging adults and caregivers of nutrients beneficial to cognition.

Funding Sources: Supported by the USDA/ARS cooperative agreement 58-8050-9-004.