Maternal high-fat diet during lactation reprograms the dopaminergic circuitry in mice
Maternal high-fat diet during lactation reprograms the dopaminergic circuitry in mice
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DOI：
10.1172/jci134412
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发表时间：
2020-07-01
影响因子：
15.9
通讯作者：
Bruening, J. C.
中科院分区：
文献类型：
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作者：
Lippert, R. N.;Hess, S.;Bruening, J. C.
母亲的围产期环境调节大脑的形成，母亲营养的改变与后代代谢和精神疾病的发展有关。在这里，我们发现，小鼠哺乳期间的母亲高脂肪饮食（HFD）喂养会引起后代多巴胺能回路中基因表达的长期变化。这转化为多巴胺能中脑神经元的沉默，减少与其下游靶标的连接，并减少纹状体中刺激诱发的多巴胺（DA）释放。尽管 DA 中脑神经元的活性减弱，但暴露于 HFD 喂养的母亲的后代表现出 DA 相关表型的性别二态性表达，即雄性过度运动，雌性增加美味食物和蔗糖的摄入量。这些表型源于 D1 中型多棘神经元 (MSN) 自发活动的同时增加和 D2 MSN 投射的大幅减少。总的来说，我们已经解开了多巴胺能回路的根本重组，这是通过在有限时间内改变母体营养来诱导后代持续行为变化的。
The maternal perinatal environment modulates brain formation, and altered maternal nutrition has been linked to the development of metabolic and psychiatric disorders in the offspring. Here, we showed that maternal high-fat diet (HFD) feeding during lactation in mice elicits long-lasting changes in gene expression in the offspring's dopaminergic circuitry. This translated into silencing of dopaminergic midbrain neurons, reduced connectivity to their downstream targets, and reduced stimulus-evoked dopamine (DA) release in the striatum. Despite the attenuated activity of DA midbrain neurons, offspring from mothers exposed to HFD feeding exhibited a sexually dimorphic expression of DA-related phenotypes, i.e., hyperlocomotion in males and increased intake of palatable food and sucrose in females. These phenotypes arose from concomitantly increased spontaneous activity of D1 medium spiny neurons (MSNs) and profoundly decreased D2 MSN projections. Overall, we have unraveled a fundamental restructuring of dopaminergic circuitries upon time-restricted altered maternal nutrition to induce persistent behavioral changes in the offspring.