Impact of early high-fat diet consumption on different systems of memory ; Impact de la consommation précoce d’un régime hyperlipidique obésogène sur différents systèmes de mémoire

Clinical and experimental studies have established that obesity, resulting mainly from consumption of energy-dense food such as high-fat diet (HFD), is associated with adverse cognitive and emotional outcomes. The prevalence of obesity during childhood and adolescence has reached epidemic levels. This is particularly worrisome since these periods are crucial for hippocampal and amygdala maturation, two brain structures necessary for shaping memory and emotional functions. It is thus critical to determine the impact of HFD exposure during these early developmental periods on memory and emotional processes. First, we show that perinatal HFD exposure (throughout gestation and lactation), leads to dendritic shrinkage of pyramidal neurons in the CA1 of the hippocampus but also in the basolateral amygdala (BLA) in adult rats. These results add to the growing literature indicating changes in hippocampal-dependent memory after perinatal HFD exposure. Regarding amygdala, perinatal HFD exposure specifically impairs odor aversion memory, a task highly dependent on BLA function, without affecting olfactory or malaise processing. These results are the first to show that perinatal HFD exposure impairs amygdala functions, at cellular and behavioral levels. Next, we investigated the cellular mechanisms underlying memory impairment induced by adolescent HFD consumption. We first show that HFD consumption from weaning to adulthood (covering adolescence) impairs long-term, but not short-term, object recognition memory (ORM) in novel context condition which was associated with higher circulating corticosterone and enhanced hippocampal endocannabinoid levels (anandamide in particular) in HFD-fed mice. Systemic post-training blockade of glucocorticoid receptors (GR) or cannabinoid receptors type 1 (CB1R) prevented HFD-induced memory deficits. These treatments also normalized training-induced c-Fos over-activation specifically in hippocampus in HFD group stressing the importance of this structure. Indeed, hippocampal CB1R deletion ...