Elsevier

Psychoneuroendocrinology

Volume 83, September 2017, Pages 49-57
Psychoneuroendocrinology

Maternal high-fat diet leads to hippocampal and amygdala dendritic remodeling in adult male offspring

https://doi.org/10.1016/j.psyneuen.2017.05.003Get rights and content

Highlights

  • Perinatal high-fat diet (HFD) induces hippocampal dendritic shrinkage at adulthood.

  • Perinatal HFD reduces dendritic complexity in basolateral amygdala.

  • Perinatal HFD impairs amygdala-dependent odor aversion memory.

  • Perinatal HFD has no impact on body weight but enhances circulating leptin.

Abstract

Early-life exposure to calorie-dense food, rich in fat and sugar, contributes to the increasing prevalence of obesity and its associated adverse cognitive and emotional outcomes at adulthood. It is thus critical to determine the impact of such nutritional environment on neurobehavioral development. In animals, maternal high-fat diet (HFD) consumption impairs hippocampal function in adult offspring, but its impact on hippocampal neuronal morphology is unknown. Moreover, the consequences of perinatal HFD exposure on the amygdala, another important structure for emotional and cognitive processes, remain to be established. In rats, we show that adult offspring from dams fed with HFD (45% from fat, throughout gestation and lactation) exhibit atrophy of pyramidal neuron dendrites in both the CA1 of the hippocampus and the basolateral amygdala (BLA). Perinatal HFD exposure also impairs conditioned odor aversion, a task highly dependent on BLA function, without affecting olfactory or malaise processing. Neuronal morphology and behavioral alterations elicited by perinatal HFD are not associated with body weight changes but with higher plasma leptin levels at postnatal day 15 and at adulthood. Taken together, our results suggest that perinatal HFD exposure alters hippocampal and amygdala neuronal morphology which could participate to memory alterations at adulthood.

Introduction

The increased prevalence of obesity has been attributed to excessive intake of calorie-dense food, in particular high-fat diets (HFD), associated with reduced physical activity (Andersen, 2000). Recent data indicate that a large proportion of childbearing women are obese (Ogden et al., 2012) suggesting that the children are exposed to calorie-dense food in utero and during their early postnatal development. Although few studies have explored this issue, clinical data suggest that maternal obesity might be associated with poor cognitive function in children (Brion et al., 2011, Tanda et al., 2013).

Experimental studies in rodents have reported cognitive changes, in particular alterations of hippocampal-dependent spatial memory, in offspring of dams fed HFD during gestation and lactation (Tozuka et al., 2010, Page et al., 2014). In line with these studies, we recently demonstrated that perinatal HFD exposure increases hippocampal vulnerability to the adverse effects of post-weaning HFD consumption on spatial memory (Lépinay et al., 2015). The remodeling of dendrites and spines represents a form of structural plasticity that has been proposed as an important mechanism supporting memory (Bailey and Kandel, 1993, Maletic-Savatic et al., 1999, Yang et al., 2008). Interestingly, maternal obesity transiently impairs dendritic arborization of newborns neurons in the hippocampal dentate gyrus of juvenile, but not adult, offspring (Tozuka et al., 2010). However it remains to determine whether perinatal HFD exposure could have lasting effects in other hippocampal subfields necessary for spatial memory such as CA1 (Tsien et al., 1996).

Another structure playing an important role in memory processes is the basolateral amygdala (BLA). Indeed, the BLA is critical for the processing of emotional memories and the production of appropriate emotional responses (LeDoux, 2007, McGaugh, 2004). Previous studies indicate that perinatal HFD alters gene expression in the amygdala (Grissom et al., 2017, Sasaki et al., 2013) but the effects on BLA neuronal morphology and on BLA-dependent cognitive processes are unknown.

In the present study, we aimed at determining the impact of perinatal exposure to HFD (throughout gestation and lactation) on morphology and spine density of CA1 and BLA pyramidal neurons in adult rats. We also investigated the impact of perinatal HFD exposure on BLA-dependent function. We focused on conditioned odor aversion (COA), based on odor-malaise pairing, as it is highly dependent on BLA integrity (Bermúdez-Rattoni et al., 1983, Bermúdez-Rattoni et al., 1986, Sevelinges et al., 2009).

Section snippets

Animals and diets

All experiments were approved by the Bioethical committee of our University (N°50120186-A) and région Aquitaine Veterinary Services (Direction Départementale de la Protection des Animaux, approval ID: A33-063-920) according to the European legislation (Directive 2010/63/EU, 2010 September 22th). Wistar rats were housed in a temperature-controlled room (22 °C) within a 12 h light/dark cycle (lights on at 8 a.m.). Unless otherwise specified, animals had access to water and food ad libitum.

Thirty

Effect of perinatal HFD exposure on body weight and metabolic parameters during development and at adulthood

Body weight of PND15 pups or adult offspring was not affected by perinatal HFD (PND15: t(13) = 1.50, n.s.; adulthood: t(17) < 1, n.s.; Fig. 1A and E). However, perinatal HFD significantly increased plasma leptin level at both PND15 and adulthood (unpaired t-test, PND15: t(16) = 2.88, p = 0.01; adulthood: t(10) = 2.49, p = 0.03; Fig. 1B and F), whereas it had no effect on glycemia (PND15: t(11) = 1.18, n.s.; adulthood: t(12) < 1, n.s.; Fig. 1C and G) or corticosterone levels in plasma (PND15: t(13) < 1, n.s.;

Discussion

Growing evidence indicates that HFD affects brain structures and functions (for review: Kanoski and Davidson, 2011). There is a window during the first postnatal weeks, especially before weaning, wherein the morphology and physiology of hippocampal and amygdala neurons undergo rapid and pronounced changes (Chareyron et al., 2012, Groen et al., 2014, Moryś et al., 1998, Rubinow et al., 2009). In particular, neurons exhibit soma and dendritic expanding during this period along with significant

Contributors

Y.J., M.R., M.D. and G.F. designed the research. Y.J., M.R. and A.M.C. conducted the research. Y.J. and M.R. analyzed data and performed statistical analyses. Y.J., M.R., M.D. and G.F. wrote the paper.

Acknowledgements

This work was supported by the French ANR-12-DSSA-0004 IBISS (MD) and the French ANR-15-CE17-0013 OBETEEN (GF). YJ was the recipient of a PhD fellowship from the Ministry of Science and Technology of Thailand (2013–2016). MR was the recipient of a PhD fellowship from the French Ministry of Research and Higher Education (2014–2017). AMC was the recipient of a Master fellowship from the Erasmus+ program (2015). The authors thank V. Nicolas, E. Roudeix and A.L. Lépinay for their help during

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