P.2.015 - The differential effects of short-term exposure to high fat diet on hippocampal function during juvenility and adulthood

Abstract

Environmental and metabolic challenges during early life can have long-term devastating effects on cognitive and emotional functions. We recently showed in two lines of experiments that the juvenile brain is different from that of the adult brain; we showed that stress has opposite effects on prefrontal cortex plasticity and extinction [1]. Specifically, while stress results in impaired long-term potentiation (LTP) and extinction in the adult animal, it resulted in enhanced extinction and LTP in the juveniles. Similarly, exposure to long-term high fat diet (HFD) from juvenility until adulthood was associated with enhanced activation and plasticity in the amygdala and impaired activation and plasticity in the hippocampus, while similar exposure starting at adulthood was not associated with these effects [2]. Both stress and HFD are associated with activation of the hypothalamic-pituitary-adrenal (HPA) axis. Based on these findings we focused on the effects of short- term exposure to HFD on synaptic plasticity in Schaffer Collateral- CA1 pathway and hippocampal-dependent spatial memory in adults [post-natal day (PND 60)] and juveniles (PND 27). Rats were exposed to HFD for 7-10 days and CA1 LTP was examined or spatial recognition. In the spatial paradigm, two different objects were located in opposite corners; each rat was allowed to explore the objects for 5 min, 24h after the sample phase the rat was presented with the same two objects one of the objects was placed at a new location. A discrimination index calculated for each animal was expressed as TN/(TN+TF) (TN = time spent exploring the object in the novel location; TF = time spent exploring the object in the familiar location). In the last part of this work we examined the ability of the glucocorticoid receptor (GR) antagonist (RU486) to reverse the effects of the HFD on LTP in the CA1 pathway and on spatial memory. The main finding of this experiment was that short-term HFD deferentially modulates plasticity in the adult animals as compared to the juveniles. Specifically, in the Schaffer Collateral- CA1 pathway, in contrast to the adult animals where exposure to short-term HFD enhanced the induction of LTP; in the juvenile animals’ exposure to the same duration of HFD inhibited LTP in the CA1. Furthermore, corresponding to these results, short-term HFD enhanced spatial memory in adult animals while it abolished spatial memory in juvenile rats. In addition, after systemic application of GRs antagonist the effects of HFD were no longer observed; the antagonist abolished the induction of LTP in the HFD-fed adults while enhancing induction in HFD-fed juveniles and reversed the HFD effects on spatial memory.The results were presented as mean ± S.E.M. For statistical analysis, independent t-test and ANOVA for repeated measures tests were used as indicated. These results suggest developmental differences in the way short-term HFD affects CA1 plasticity and the spatial memory. These effects are differently modulated by GRs; inhibition of GRs normalized the potentiation in CA1. These effects of HFD may be relevant to the increase prevalence of emotional and behavioral disorders in children exposed to western diet.