Cognitive Impairment Due to Leptin Withdrawal in Rat Offspring of Dams with Maternal Diet-Induced Obesity

BACKGROUND: Obesity during pregnancy is a potential threat to the health and neurodevelopment of the offspring. This study investigated the effect of maternal diet-induced obesity (DIO) on the cognitive abilities of the offspring in rats. MATERIAL/METHODS: Female Sprague-Dawley rats were fed a high-fat diet to induce obesity, and the leptin levels in dams and offspring were evaluated using ELISA. The effect of DIO on the learning and memory in offspring was measured using electrophysiology and the Morris water maze test. In addition, the expression of molecules related to synaptic plasticity was investigated. Furthermore, the effect of leptin on neuronal cells was investigated, and the influence of leptin on the regulation of calcium current activity was evaluated in vitro. RESULTS: Results showed that DIO dams had increased leptin levels during gestation, and offspring had drastically decreased leptin levels after delivery. The cognitive ability of offspring with maternal DIO was mildly impaired after delivery. Furthermore, long-term potentiation in DIO neonatal offspring was lower than in the control group at 2–3 weeks old; decreased expression of the leptin receptor was accompanied by N-methyl-D-aspartate receptor (NMDAR) downregulation during neonatal development. In addition, it was demonstrated that leptin enhanced NMDAR activity and promoted calcium current activity in a concentration-dependent manner. CONCLUSIONS: The results indicated that the neonatal offspring of DIO dams showed cognitive impairment during neonatal development, which may be attributed to leptin withdrawal.