Maternal and postweaning high-fat diets disturb hippocampal gene expression, learning, and memory function

Abstract

We tested the hypothesis that excess saturated fat consumption during pregnancy, lactation, and/or postweaning alters the expression of genes mediating hippocampal synaptic efficacy and impairs spatial learning and memory in adulthood. Dams were fed control chow or a diet high in saturated fat before mating, during pregnancy, and into lactation. Offspring were weaned to either standard chow or a diet high in saturated fat. The Morris Water Maze was used to evaluate spatial learning and memory. Open field testing was used to evaluate motor activity. Hippocampal gene expression in adult males was measured using RT-PCR and ELISA. Offspring from high fat-fed dams took longer, swam farther, and faster to try and find the hidden platform during the 5-day learning period. Control offspring consuming standard chow spent the most time in memory quadrant during the probe test. Offspring from high fat-fed dams consuming excess saturated fat spent the least. The levels of mRNA and protein for brain-derived neurotrophic factor and activity-regulated cytoskeletal-associated protein were significantly decreased by maternal diet effects. Nerve growth factor mRNA and protein levels were significantly reduced in response to both maternal and postweaning high-fat diets. Expression levels for the N-methyl-d-aspartate receptor (NMDA) receptor subunit NR2B as well as synaptophysin were significantly decreased in response to both maternal and postweaning diets. Synaptotagmin was significantly increased in offspring from high fat-fed dams. These data support the hypothesis that exposure to excess saturated fat during hippocampal development is associated with complex patterns of gene expression and deficits in learning and memory.

Effects of high-fat diet exposure on learning & memory

“…Finally, while the specific contributions of prenatal versus early postnatal exposure to HF diet has not been well established, results from our own cross-fostering experiments suggest that exposure at either time is sufficient to induce impairment in both Novel Object Recognition and the Barnes Maze among adult offspring [138], which, in rats, is consistent with the trajectory of hippocampal development that spans both the prenatal and early postnatal periods [139–141]. Regarding potential mechanisms underlying these changes, maternal HF diet consumption has been found to increase hippocampal inflammation [126], increase plasma leptin [127], and decrease hippocampal BDNF [134,135], while alterations in placental transport of nutrients and hormones may also be involved [125]. In our own lab, we have found that maternal HF diet exposure results in offspring with decreased hippocampal gene expression of insulin receptor ( Insr ), leptin receptor ( Lepr ), and glucose transporter 1 ( Slc2a1 ) at weaning.…”

“…Prior work in our lab using a rat model has found that maternal exposure to a 60% HF diet increases the offspring’s risk of developing diet-induced obesity [130], while also altering leptin sensitivity [131], and ingestive behavior [132,133]. Further, several behavioral studies in mice and rats have found that maternal consumption of various HF diets can result in impairment in the Morris Water Maze [126,134] and Barnes Maze [135]. Two other studies in rats found Morris Water Maze impairment among offspring born to HF fed dams that were then continued on a HF diet after weaning [136,137].…”

Maternal High-Fat Diet Modifies the Immature Hippocampus Vulnerability to Perinatal Asphyxia in Rats

“…The female rats received the HFD shortly after weaning, mimicking a potential harmful maternal dietary habit, known to impact embryogenesis and fetal development [1][2][3][4][5][6], aspects which were not examined in this study. Our aim was to specifically investigate a potential cumulative detrimental effect of maternal HFD on offspring exposed to asphyxia.…”

“…One of the most vulnerable brain areas affected by HFD is the hippocampus, resulting in a delayed utero development [5], learning and memory impairment, and addiction-like behaviors [6]. The mechanisms involved are exacerbated proliferation of astrocytes, increased stress response to acute stimuli [7], and altered development of the placental vasculature [8].…”

Maternal high-fat diet influences stroke outcome in adult rat offspring

“…Exposure to early maltreatment has been reported to induce long-lasting changes in the methylation of the Bdnf gene in the prefrontal cortex in mice (Roth et al 2009). Furthermore, Page et al (2014) demonstrated that maternal fat-rich diet significantly decreases the levels of BDNF mRNA. Therefore, there is no reason to exclude the possibility that maternal HFD feeding may program the HPA system and BDNF expression and ultimately alter adult offspring susceptibility to ischemic stroke.…”