The adipocyte hormone leptin sets the emergence of hippocampal inhibition in mice.
The adipocyte hormone leptin sets the emergence of hippocampal inhibition in mice.
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DOI：
10.7554/elife.36726
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发表时间：
2018-08-14
期刊：
影响因子：
7.7
通讯作者：
Gaiarsa JL
中科院分区：
文献类型：
--
作者：
Dumon C;Diabira D;Chudotvorova I;Bader F;Sahin S;Zhang J;Porcher C;Wayman G;Medina I;Gaiarsa JL
大脑的计算依赖于在啮齿动物出生后发育过程中逐渐出现的兴奋和抑制之间的适当平衡。γ-氨基丁酸(GABA)神经传递支持成年大脑的抑制，但兴奋未成熟的啮齿动物神经元。GABA开关时间的改变会导致神经疾病，因此公布相关的调节器可能是一个有希望的治疗策略。在这里，我们表明，脂肪细胞激素瘦素设定了在新生啮齿动物海马区出现GABA能抑制的节奏。在缺乏瘦素信号的情况下，海马神经元表现出GABA能抑制的提前出现。相反，母体肥胖与高瘦素血症相关，推迟了子代GABA从兴奋性到抑制性的转换。这项研究揭示了瘦素的发育功能，可能与神经疾病的发病机制有关，并有助于理解母体环境如何对后代大脑发育产生不利影响。
Brain computations rely on a proper balance between excitation and inhibition which progressively emerges during postnatal development in rodent. γ-Aminobutyric acid (GABA) neurotransmission supports inhibition in the adult brain but excites immature rodent neurons. Alterations in the timing of the GABA switch contribute to neurological disorders, so unveiling the involved regulators may be a promising strategy for treatment. Here we show that the adipocyte hormone leptin sets the tempo for the emergence of GABAergic inhibition in the newborn rodent hippocampus. In the absence of leptin signaling, hippocampal neurons show an advanced emergence of GABAergic inhibition. Conversely, maternal obesity associated with hyperleptinemia delays the excitatory to inhibitory switch of GABA action in offspring. This study uncovers a developmental function of leptin that may be linked to the pathogenesis of neurological disorders and helps understanding how maternal environment can adversely impact offspring brain development.