Maternal nutritional programming by caloric exposure during pregnancy and lactation results in long-term behavioral modification in the offspring. Here, we characterized the effect of maternal caloric exposure on synaptic and brain morphological organization and its effects on depression-like behavior susceptibility in rats’ offspring. Female Wistar rats were exposed to chow or cafeteria (CAF) diet for 9 weeks (pre-pregnancy, pregnancy, and lactation) and then switched to chow diet after weaning. By postnatal day 60, the male Wistar rat offspring were tested for depressive-like behavior using operational conditioning, novelty suppressed feeding, sucrose preference, and open-field test. Brain macro and microstructural morphology were analyzed using magnetic resonance imaging deformation-based morphometry (DBM) and western blot, immunohistochemistry for NMDA and AMPA receptor, synaptophysin and myelin, respectively. We found that the offspring of mothers exposed to CAF diet displayed deficient motivation showing decrease in the operant conditioning, sucrose preference, and suppressed feeding test. Macrostructural DBM analysis showed reduction in the frontomesocorticolimbic circuit volume including the nucleus accumbens (NAc), hippocampus, and prefrontal cortex. Microstructural analysis revealed reduced synaptic terminals in hippocampus and NAc, whereas increased glial fibrillary acidic protein in hippocampus and lateral hypothalamus, as well as a decrease in the hippocampal cell number and myelin reduction in the dentate gyrus and hilus, respectively. Also, offspring exhibited increase of the GluR1 and GLUR2 subunits of AMPA receptor, whereas a decrease in the mGluR2 expression in hippocampus. Our findings reveal that maternal programming might prime depression-like behavior in the offspring by modulating macro and micro brain organization of the frontomesocorticolimbic circuit.

通过怀孕和哺乳期间的热量摄入进行的母亲营养规划会导致后代的长期行为改变。在这里，我们描述了母体热量暴露对突触和大脑形态组织的影响及其对大鼠后代抑郁样行为易感性的影响。雌性 Wistar 大鼠接受食物或食堂 (CAF) 饮食 9 周（怀孕前、怀孕和哺乳期），然后在断奶后转为食物饮食。到出生后第 60 天，使用操作调节、新奇抑制喂养、蔗糖偏好和旷场测试对雄性 Wistar 大鼠后代进行抑郁样行为测试。分别使用基于磁共振成像变形的形态测定法 (DBM) 和蛋白质印迹、免疫组织化学对 NMDA 和 AMPA 受体、突触素和髓鞘质分析脑宏观和微观结构形态。我们发现，接受 CAF 饮食的母亲的后代表现出动机不足，表现出操作性条件反射、蔗糖偏好和抑制喂养测试的减少。宏观结构 DBM 分析显示额中皮质边缘回路体积减少，包括伏隔核 (NAc)、海马和前额皮质。微观结构分析显示，海马和 NAc 中的突触末梢减少，而海马和下丘脑外侧的胶质纤维酸性蛋白增加，以及齿状回和门中的海马细胞数量减少和髓磷脂减少。此外，后代的 AMPA 受体 GluR1 和 GLUR2 亚基增加，而海马 mGluR2 表达减少。我们的研究结果表明，母体编程可能通过调节额中皮质边缘回路的宏观和微观大脑组织来引发后代的抑郁样行为。