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孕期摄入致肥胖饮食会使后代的突触可塑性异常,并使其对美味食物产生类似成瘾的行为。

Obesogenic diet intake during pregnancy programs aberrant synaptic plasticity and addiction-like behavior to a palatable food in offspring.

作者信息

Camacho Alberto, Montalvo-Martinez Larisa, Cardenas-Perez Robbi E, Fuentes-Mera Lizeth, Garza-Ocañas Lourdes

机构信息

Department of Biochemistry, Universidad Autonoma de Nuevo Leon, Facultad de Medicina, Monterrey, Mexico; Neurometabolism Unit, Center for Research and Development in Health Sciences, Universidad Autonoma de Nuevo Leon, Monterrey, Mexico.

Department of Biochemistry, Universidad Autonoma de Nuevo Leon, Facultad de Medicina, Monterrey, Mexico; Neurometabolism Unit, Center for Research and Development in Health Sciences, Universidad Autonoma de Nuevo Leon, Monterrey, Mexico.

出版信息

Behav Brain Res. 2017 Jul 14;330:46-55. doi: 10.1016/j.bbr.2017.05.014. Epub 2017 May 6.

Abstract

Contextual food conditioned behaviors require plasticity of glutamatergic neurotransmission in the reward system, involving changes in the expression of including a-amino-3-hydroxy-5-methylisoxazole 4-propionate receptors (AMPA), N-methyl-d-aspartic acid (NMDA) and metabotropic glutamate 2,3 (mGlur 2,3). However, the role of changes in glutamatergic synaptic markers on energy-dense palatable food preference during development has not been described. Here, we determine the effect of nutritional programing during gestation on fat food choices using a conditioned place preference (CPP) test and an operant training response and its effect on glutamatergic markers in the nucleus accumbens (Nac) shell and prefrontal cortex (PFC). Our data showed that rats displayed preference for palatable fat food and an increase in caloric intake when compared to a chow diet. Notably, 74% of rats showing a preference for fat food intake correlate with a positive HFD-paired score whereas 26% failed to get HFD-conditioned. Also, male rats trained under an operant training response schedule (FR1, FR5 and PR) showed high and low responder groups to work for food. Notably, hypercaloric nutritional programing of female rats leads to exacerbation for reinforcers in female offspring compared to offspring from chow diet. Finally, we found that an operant training response to palatable reinforcers correlates with upregulation of mGlur 2,3 in the NAc shell and PFC of male rats and female offspring. Also, we found selective Nr1 upregulation in NAc shell and the PFC of female offspring. Our data suggest that nutritional programing by hypercaloric intake leads to incentive motivation to work for food and synaptic plasticity alteration in the mesolimbic system.

摘要

情境性食物条件行为需要奖赏系统中谷氨酸能神经传递的可塑性,这涉及包括α-氨基-3-羟基-5-甲基异恶唑-4-丙酸受体(AMPA)、N-甲基-D-天冬氨酸(NMDA)和代谢型谷氨酸受体2、3(mGlur 2、3)表达的变化。然而,发育过程中谷氨酸能突触标记物变化对高能美味食物偏好的作用尚未见描述。在此,我们使用条件性位置偏爱(CPP)试验和操作性训练反应来确定孕期营养编程对高脂食物选择的影响及其对伏隔核(Nac)壳和前额叶皮质(PFC)中谷氨酸能标记物的影响。我们的数据显示,与普通饮食相比,大鼠对美味高脂食物表现出偏爱且热量摄入增加。值得注意的是,74%表现出对高脂食物摄入偏爱的大鼠与高脂饮食配对阳性得分相关,而26%未形成高脂饮食条件化。此外,在操作性训练反应模式(FR1、FR5和PR)下训练的雄性大鼠表现出高反应组和低反应组以获取食物。值得注意的是,与普通饮食后代相比,雌性大鼠的高热量营养编程导致雌性后代对强化物的反应加剧。最后,我们发现对美味强化物的操作性训练反应与雄性大鼠和雌性后代伏隔核壳和前额叶皮质中mGlur 2、3的上调相关。此外,我们在雌性后代的伏隔核壳和前额叶皮质中发现了选择性Nr1上调。我们的数据表明,高热量摄入的营养编程导致为获取食物的动机激励和中脑边缘系统的突触可塑性改变。

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