Diet and the brain. A view from basic biomedicine

BEAUQUIS J

Mar del Plata

Congreso; Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2018

Sociedad Argentina de Investigación Clínica

In the last few years, increased attention has been put in understanding the modulatory role of diet on the central nervous system. On the one hand, epidemiological evidence suggests that consumption of ?western diets? (high intake of fat, carbohydrates and industrially processed food) constitutes a risk factor for neurodegenerative and neurovascular disorders. On the other hand, evidence shows that dietary restriction (DR) ameliorates the impact of age-associated diseases, such as Alzheimer?s (AD). However, underlying mechanisms are not clear yet and could involve the modulation of multiple biological pathways. Our objective is to describe and understand histological, biochemical and molecular consequences in the brain and associated behavioral changes in response to A) the consumption of a high-fat diet (HFD) and B) dietary restriction in animal models. Our results show that C57BL/6 mice that were fed a moderately HFD (45% of kCal from fat vs. 12% in control diet) since weaning displayed peripheral and central inflammation along with impaired insulin signaling without overweight. Cognitive deficits were found in HFD mice, concomitantly with decreased hippocampal adult neurogenesis. Using an in vitro model of fatty acid exposure on microglia we found that secreted exosomes, as a mean for intercellular communication, induced dendritic remodeling on primary hippocampal neurons. Finally, using a transgenic model of AD we studied the neuroprotective capability of periodic DR. We found that DR for 6 weeks was associated with decreased activation of hippocampal microglia, increased neurogenesis and reversal of cognitive impairment in AD mice. We studied the communication between astrocytes and microglia in vitro and found that astrocytes under nutrient restriction are able to prevent amyloid-induced microglial activation. Our results suggest that diet has a significant role on brain function and structure, with degenerative or protective effects, and that glial cells are possible effector cells and potential therapeutic targets.