Department of Biochemistry, College of Medicine, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, NL, México.
Neurometabolism Unit, Center for Research and Development in Health Sciences, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, NL, México.
Transl Psychiatry. 2021 Jan 14;11(1):53. doi: 10.1038/s41398-020-01157-x.
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.
孕期和哺乳期的热量暴露会导致母体营养编程，从而使后代的行为长期发生改变。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，以及其对大鼠后代抑郁样行为易感性的影响。雌性 Wistar 大鼠在怀孕前、怀孕期间和哺乳期接受标准饮食或自助餐（CAF）饮食 9 周，然后在断奶后切换到标准饮食。在产后第 60 天，使用操作性条件反射、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。使用磁共振成像变形测量（DBM）和 Western blot、NMDA 和 AMPA 受体的免疫组织化学、突触小体和髓鞘分别分析大脑宏观和微观结构形态。我们发现，暴露于 CAF 饮食的母亲的后代表现出动机不足，表现为操作性条件反射、蔗糖偏好和抑制喂养测试减少。宏观 DBM 分析显示，包括伏隔核（NAc）、海马体和前额叶皮层在内的额皮质边缘回路体积减少。微观结构分析显示海马体和 NAc 中的突触末梢减少，而海马体和外侧下丘脑的神经胶质纤维酸性蛋白增加，以及海马体中的细胞数量减少和齿状回和门区的髓鞘减少。此外，后代表现出 AMPA 受体的 GluR1 和 GLUR2 亚基增加，而海马体中 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皮质边缘回路的宏观和微观大脑组织，使后代产生抑郁样行为。
