Acute exposure to a high-fat diet in juvenile male rats disrupts hippocampal-dependent memory and plasticity through glucocorticoids

Tala Khazen,Guillaume Ferreira,Ossama A. Hatoum,Mouna Maroun

doi:10.1038/s41598-019-48800-2

Abstract

The limbic circuit is still undergoing maturation during juvenility and adolescence, explaining why environmental and metabolic challenges during these developmental periods can have specific adverse effects on cognitive functions. We have previously shown that long-term exposure (8–12 weeks) to high-fat diet (HFD) during adolescence (from weaning to adulthood), but not at adulthood, was associated with altered amygdala and hippocampal functions. Moreover, these HFD effects were normalized by treatment with glucocorticoid receptor (GR) antagonists. Here, we examined in male rats whether acute exposure (7–9 days) to HFD during juvenility [from postnatal day (PND) 21 to PND 28–30] or adulthood (from PND 60 to PND 67–69) is sufficient to affect hippocampal functions and whether it is also dependent on GRs activation. Juvenile HFD abolished both hippocampal synaptic plasticity, assessed through in vivo long-term potentiation (LTP) in CA1, and long-term hippocampal-dependent memory, using object location memory (OLM). No effect of HFD was observed in short-term OLM suggesting a specific effect on consolidation process. In contrast, adult HFD enhanced in vivo LTP and OLM. Systemic application of GR antagonist alleviated HFD-induced LTP and OLM impairments in juveniles. These results suggest that acute exposure to HFD during juvenility is sufficient to impair hippocampal functions in a GR-dependent manner. Interestingly, this effect depends on the developmental period studied as acute exposure to HFD at adulthood did not impair, but rather enhanced, hippocampal functions.

Highlights

Neuroscience & Biobehavioral Reviews 53, 37–51 (2015). 29
We monitored the consumption of highfat diet (HFD) on bodyweight change and did not find any significant differences between the animals that were exposed to HFD as juveniles or adults and their corresponding controls exposed to the regular diet [jCD or aCD; F(1, 22) < 1 for the effect of Diet; Table 1, see26]
As only the HFD-fed juveniles showed changes in plasma cort levels following exposure to the new open field and plasticity and memory impairments, we focused on juveniles and evaluated whether blocking glucocorticoid receptor (GR) could improve the effects of acute jHFD on object location memory (OLM) and long-term potentiation (LTP)

Summary

Methods

The experiments were performed using juvenile (28–30 days old) and adult (~70 days old) male Sprague Dawley rats from the local animal colony at the Haifa University. The juvenile animals were separated from the dam at the age of 21 days. Animals were housed in Plexiglas cages (4–5 rats per cage) and are maintained on a free feeding regimen and a 12 h light/dark cycle. Juvenile animals were exposed to the regular and standard chow diet, thereafter named control diet (CD) offering 3 kcal/g [consisting of 4% fat and 60% carbohydrate (35% kcal) (ENVIGO, Israel)], or to HFD offering 5.2 kcal/g [consisting of 35% fat, mostly saturated fat from lard (60% kcal), and 26% carbohydrate (20% kcal) (D12492, Research Diets, New Brunswick, NJ)] from post-natal day (PND) 21 to PND 28. Adult animals were exposed to CD or HFD from PND 60 to PND 67–69. Animals were kept on the respective diet until the end of the behavioral or electrophysiological experiments

Results

Discussion

Conclusion