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

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.

Figure 1

Opposite effects of acute exposure (7 days) to HFD on object location memory (OLM) in juvenile and adult male rats (A) Schematic representation of the experimental procedure. (B) A significant interaction between diet and age of exposure was observed in the long-term OLM [F(1, 20) = 23.7, P < 0.001]. Whereas acute exposure to HFD impaired long-term OLM in juvenile rats (***P = 0.001), HFD enhanced OLM in adults (⁺P = 0.075). (C) No significant effects were observed between the groups in the short-term OLM [F(1, 32) = 1.4].

Figure 2

Opposite effects of acute exposure (7 days) to HFD on hippocampal plasticity in juvenile and adult male rats. (A) Schematic representation of the experimental procedure. (B) Time course plots of normalized field post-synaptic potentials (fPSPs) recorded in vivo before and after theta burst stimulation (TBS) of the Schaffer collateral-CA1 pathway. (C) Bar histogram representing percentage of long-term potentiation (LTP) during the 40 min after TBS in the same groups as described in (B). A significant interaction between diet and age of exposure was observed [F(1, 19) = 24.8, P < 0.001] with exposure to HFD impairing LTP in juvenile animals (***P = 0.002) whereas in adults, HFD exposure enhanced LTP (*P = 0.04).

Figure 3

Effects of acute exposure (7 days) to HFD on glucocorticoid receptor (GR) expression in hippocampus and novelty-induced plasma corticosterone release in juvenile and adult rats. (A) Schematic representation of the experimental procedure. (B) Acute exposure to HFD did not affect the levels of GR expression in CA1 in either juvenile [t(10) < 1] or adult rats [t(11) < 1]. (C) Plasma corticosterone increased after exposure to new object in a new open field (New) in HFD-fed juvenile animals [F(1, 20) = 4.9; *P < 0.05] but not in CD group [F(1, 14) = 1.1, n.s]. (D) No significant differences in levels of plasma corticosterone were observed in adult animals [F(1, 28) = 0.70, n.s].

Figure 4

Effects of glucocorticoid receptors blockade on juvenile HFD-induced impairments of object location memory and hippocampal plasticity. (A) Schematic representation of the experimental procedure. (B) HFD impaired long-term OLM in vehicle (Veh)-treated juveniles, and GR blockade with RU486 (RU) rescued OLM in the HFD group without affecting OLM in CD groups [Interaction Drug × Diet: F(1, 32) = 9.15 ***P = 0.005]. (C) Time course plots of normalized field post-synaptic potentials (fPSPs) recorded in vivo before and after theta burst stimulation (TBS) of the Schaffer collateral-CA1 pathway. (D) Bar histogram representing percentage of long-term potentiation (LTP) during the 40 min after TBS in the same groups as described in (B). HFD impaired LTP in Veh-treated juveniles, whereas prior with RU treatment in HFD fed animals restored LTP [t(14) = 3.6, ***P = 0.005]. Similarly, RU also impaired the induction of LTP in CD animals [t(2) = 5.0, P = 0.001].