EARLY EXPOSURE TO A HIGH FAT DIET PRODUCES METABOLIC AND BEHAVIORAL ALTERATIONS ASSOCIATED TO HIPPOCAMPAL NEUROINFLAMMATION AND IMPAIRED NEUROGENESIS IN C57BL/6 MICE

ANGELES VINUESA; CARLOS POMILIO; MARTÍN MENAFRA; FERNANDO BRITES; MARÍA MARTA BONAVENTURA; VICTORIA LUX-LANTOS; JUAN BEAUQUIS; FLAVIA E. SARAVIA

Congreso; 9th IBRO World Congress of Neuroscience; 2015

BackgroundThe incidence of metabolic disorders including obesity, T2 diabetes and metabolic syndrome has seriously increased in the last decades. These morbidities constitute major risk factors for neurodegenerative disorders such as Alzheimer?s disease (AD), which has a growing impact in modern societies. Several studies report that insulin resistance, impaired insulin signaling and inflammation promote cognitive impairment playing an essential role in the development of AD pathology.AimsEstablish a murine model of high fat diet (HFD) induced moderate obesity. Assess the behavioral profile of HFD mice and characterize central alterations in limbic structures.Explore the molecular mechanisms involved in the interaction of both metabolic and neurodegenerative pathologies.MethodsC57BL/6 male mice were given either a control diet CD (12% Kcal from fat) or HFD (45% kcal from fat) for 18 weeks since a week post weaning. Body weight and food consumption were registered weekly and behavioral tests were performed by the end of the treatment, from the 15th week onwards in a suitable room within housing facilities.Trunk blood, brain, liver and pancreas where rapidly extracted after decapitation. Determination of lipids, glucose and pancreatic insulin was done after a 6 hour fast.Results HFD produces metabolic alterations along with changes in behavior and central parameters. HFD mice present elevated insulin levels, dyslipidemia and increased lipid content in hepatocytes. Alterations in the behavioral profile of HFD group are shown by a set of different tests. A general alteration seen in the impediment in the Nest Building Test; deficiencies in short and mid-term spatial memory assessed with the Novel Object Localization Recognition test and Y maze test, respectively; anxious behavior in the Elevated Plus Maze and depressive- like behavior in the Tail Suspension Test. Among the central parameters, we found that the neurogenic ability is altered in HFD mice. Studying immunostaining for Ki67 and DCX, we found a decreased proliferation of neural progenitors and altered differentiation of immature neurons in the dentate gyrus of the hippocampus in HFD mice. Moreover, a greater density of microglial cells was found in the hilus of HDF mice, identified as Iba1+ cells. These cells exhibited an enlarged soma in the hilus and stratum radiatum, evidencing a potential inflammatory response in the hippocampus due to HFD. Additionally, HFD show a larger number of c-Fos+ nuclei in the amygdala, meaning an increased neural activity in this structure mostly related to emotions, mood and fear.ConclusionsOur data portrays a set of alterations in behavior and central parameters as a consequence of an early exposure to a moderate high fat diet, many of which can resemble AD-like pathologies. This fact highly motivates the need to study how metabolic and neurodegenerative disorders are interrelated in deep.