Maternal high‐sugar diet results in NMDA receptors abnormalities and cognitive impairment in rat offspring

Apr 15, 2021FASEB journal : official publication of the Federation of American Societies for Experimental Biology

High-sugar diet in mother leads to changes in brain receptors and learning problems in rat offspring

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Abstract

A maternal high-sugar diet can affect offspring memory processes by disrupting NMDA receptor composition.

Exposure to excess sugar in maternal diets during pregnancy and lactation is associated with altered memory in offspring.
Impaired recognition memory was observed in adolescent males, while spatial memory was affected in females.
NMDA receptor hypofunction and abnormal subunit composition were confirmed in the medial prefrontal cortex of adolescent offspring.
In young adults, GluN2A-containing NMDA receptors predominated in the medial prefrontal cortex, whereas GluN2B subunit contribution was higher in the hippocampus.

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Cognitive impairment affects patients suffering from various neuropsychiatric diseases, which are often accompanied by changes in the glutamatergic system. Epidemiological studies indicate that predispositions to the development of neuropsychiatric diseases may be programmed prenatally. Mother's improper diet during pregnancy and lactation may cause fetal abnormalities and, consequently, predispose to diseases in childhood and even adulthood. Considering the prevalence of obesity in developed countries, it seems important to examine the effects of diet on the behavior and physiology of future generations. We hypothesized that exposure to sugar excess in a maternal diet during pregnancy and lactation would affect memory as the NMDA receptor-related processes. Through the manipulation of the sugar amount in the maternal diet in rats, we assessed its effect on offspring's memory. Then, we evaluated if memory alterations were paralleled by molecular changes in NMDA receptors and related modulatory pathways in the prefrontal cortex and the hippocampus of adolescent and young adult female and male offspring. Behavioral studies have shown sex-related changes like impaired recognition memory in adolescent males and spatial memory in females. Molecular results confirmed an NMDA receptor hypofunction along with subunit composition abnormalities in the medial prefrontal cortex of adolescent offspring. In young adults, GluN2A-containing receptors were dominant in the medial prefrontal cortex, while in the hippocampus the GluN2B subunit contribution was elevated. In conclusion, we demonstrated that a maternal high-sugar diet can affect the memory processes in the offspring by disrupting the NMDA receptor composition and regulation in the medial prefrontal cortex and the hippocampus.

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Maternal high‐sugar diet results in NMDA receptors abnormalities and cognitive impairment in rat offspring

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