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首页> 外文期刊>American Journal of Physiology >High-fat diets induce changes in hippocampal glutamate metabolism and neurotransmission
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High-fat diets induce changes in hippocampal glutamate metabolism and neurotransmission

机译：高脂饮食会引起海马谷氨酸代谢和神经传递的改变

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Obesity and high-fat (HF) diets have a deleterious impact on hip-pocampal function and lead to impaired synaptic plasticity and learn-ing deficits. Because all of these processes need an adequate gluta-matergic transmission, we have hypothesized that nutritional imbalance triggered by these diets might eventually concern gluta-mate (Glu) neural pathways within the hippocampus. Glu is withdrawn from excitatory synapses by specific uptake mechanisms involving neuronal (EAAT-3) and glial (GLT-1, GLAST) transporters, which regulate the time that synaptically released Glu remains in the extracellular space and, consequently, the duration and location of postsynaptic receptor activation. The goal of the present study was to evaluate in mouse hippocampus the effect of a short-term high-fat dietary treatment on 1) Glu uptake kinetics, 2) the density of Glu carriers and Glu-degrading enzymes, 3) the density of Glu receptor subunits, and 4) synaptic transmission and plasticity. Here, we show that HF diet triggers a 50% decrease of the Michaelis-Menten constant together with a 300% increase of the maximal velocity of the uptake process. Glial Glu carriers GLT-1 and GLAST were upregulated in HF mice (32 and 27%, respectively), whereas Glu-degrading enzymes glutamine synthase and GABA-decarboxilase appeared to be down-regulated in these animals. In addition, HF diet hippocampus displayed diminished basal synaptic transmission and hindered NMDA-induced long-term depression (NMDA-LTD). This was coincident with a reduced density of the NR2B subunit of NMD A receptors. All of these results are compatible with the development of leptin resistance within the hippocampus. Our data show that HF diets upregulate mechanisms involved in Glu clearance and simultaneously impair Glu metabolism. Neurochemical changes occur concomitantly with impaired basal synaptic transmission and reduced NMDA-LTD. Taken together, our results suggest that HF diets trigger neurochemical changes, leading to a desensitization of NMDA receptors within the hippocampus, which might account for cognitive deficits.
机译：肥胖和高脂（HF）饮食对海马功能具有有害影响，并导致突触可塑性受损和学习不足。因为所有这些过程都需要足够的谷氨酸能传递，所以我们假设这些饮食引发的营养失衡最终可能与海马内的谷氨酸（Glu）神经通路有关。 Glu通过涉及神经元（EAAT-3）和神经胶质（GLT-1，GLAST）转运蛋白的特定摄取机制从兴奋性突触中退出，它们调节突触释放的Glu保留在细胞外空间的时间，并因此调节其持续时间和位置。突触后受体激活。本研究的目的是评估小鼠海马短期高脂饮食治疗对1）Glu吸收动力学，2）Glu载体和Glu降解酶的密度，3）Glu密度的影响。受体亚基，以及4）突触传递和可塑性。在这里，我们表明，HF饮食会触发Michaelis-Menten常数降低50％，同时最大摄取速度提高300％。在HF小鼠中，胶质细胞Glu载体GLT-1和GLAST被上调（分别为32％和27％），而在这些动物中，Glu降解酶谷氨酰胺合酶和GABA-去羧化酶似乎被下调。此外，HF饮食海马显示出减少的基础突触传递，并阻碍了NMDA引起的长期抑郁症（NMDA-LTD）。这与NMD A受体的NR2B亚基密度降低相吻合。所有这些结果与海马内瘦素抵抗的发展是相容的。我们的数据表明，HF饮食会上调参与Glu清除的机制，同时损害Glu的代谢。神经化学变化伴随基底突触传递受损和NMDA-LTD降低而发生。两者合计，我们的结果表明，HF饮食会触发神经化学变化，导致海马内NMDA受体脱敏，这可能是认知缺陷的原因。

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