Diet-induced changes in brain structure and behavior in old gerbils

BACKGROUND/OBJECTIVES: Aging is associated with many physiological alterations such as changes in metabolism, food intake and brain dysfunction. Possible ways to correct age-related brain dysfunction using dietary treatments still remains undeveloped. The aim of our research was to investigate whether long-term dietary treatment with 2-oxoglutarate (2-OX), which is involved in many regulatory pathways, together with pancreatic-like enzymes of microbial origin (PLEM), which ensure appropriate digestion and absorption of nutrients, affects age-related changes in the brain morphology and cognitive function in old Mongolian gerbils. MATERIALS/METHODS: Experiment was comprised of two separate studies. Samples of the hippocampus were obtained from male Mongolian gerbils of different ages (n=63 in the first study, n=74 in the second study). Immunohistochemistry was used for visualization of the nestin/NeuN-positive neuronal progenitors. Changes in amount of neural cell adhesion molecules (NCAMs) were estimated using enzyme-linked immunosorbent assay. For assessment of cognitive and sensorimotor functions, the T-maze spontaneous alternation test and the adhesive removal test (ART) were used. The ultrastructure of the CA1 hippocampal area was visualized using transmission electron microscopy. RESULTS: Long-term treatment with 2-OX+PLEM led to a significantly increased amount of nestin/NeuN-positive cells in the CA1 hippocampal area and positive changes in learning and sensorimotor functions. As for synaptic transmission, changes in the spatial distribution of synaptic vesicles, as well as the redistribution of NCAM forms, were observed in the hippocampal synapses of the old gerbils. CONCLUSIONS: Taken together, our data show that dietary supplementation with 2-OX+PLEM not only enhances the proliferation and differentiation of neuronal progenitors, but also improves age-related deficits in the morphological and functional state of the brain of old gerbils. Thus, suggesting that a 2-OX+PLEM-enriched diet could also improve brain functions that have deteriorated with age.