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