High fat diet promotes cognitive impairment, neuroinflammation and decreased hippocampal plasticity: role of microglial exosomes

VINUESA A; BENTIVEGNA M; CALFA, G; FILIPELLO F; POMILIO C; GREGOSA A; PRESA J; MATTEOLI M; BEAUQUIS J; SARAVIA F

Montreal

Congreso; ISN-ASN Meeting Montreal 2019; 2019

ISN-ASN

Western dietary habits including high fat foods are increasingly represented in juvenile populations, and constitute one of the factors that affect brain health, potentially leading to long lasting effects. The aim of this study was to assess the impact of an early exposure to a high fat diet (HFD) on mouse hippocampal plasticity. C57BL/6J male mice were exposed to HFD for 6 weeks since weaning. Glucose and IL1β levels were found to be higher in serum of HFD mice, without overweight. In the hippocampus, neuroinflammation was evidenced by Iba1+ cells reactivity and increased expression of TNFα and IL1β in HFD group, which also exhibited a strongly reduced neurogenic capability: decreased Ki67+ cells and immature DCX+ neurons in the SGZ of the dentate gyrus. We also found a reduced proportion of mature Dil‐labeled dendritic spines from CA1 neurons and diminished levels of the scaffold protein Shank2, suggesting a defective connectivity. Moreover, HFD mice exhibited spatial memory alterations in the novel object location recognition test. To study whether microglia could be mediating HFD‐associated neuronal changes, primary microglia was incubated with palmitate, a saturated fatty acid present in HFD. Palmitate induced a proinflammatory profile as shown by secreted cytokine levels and exosome‐like extracellular vesicles that were able to induce an immature dendritic spine phenotype in primary GFP+ hippocampal neurons, in line with the in vivo findings. These results provide novel data concerning microglia‐neuron communication and highlight that fat excess during an early period of life could negatively impact on hippocampal plasticity in a neuroinflammatory context, where microglia‐derived exosomes could be directly implicated.