Leptin, the obese gene product, rapidly modulates synaptic transmission in the hypothalamus.

Leptin, the obese gene product, rapidly modulates synaptic transmission in the hypothalamus.
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DOI:
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发表时间:
1996-08
影响因子:
3.6
通讯作者:
S. Glaum;Manami Hara;V. Bindokas;Chong C. Lee;Kenneth S. Polonsky;Graeme I. Bell;Richard J. Miller
S. Glaum;Manami Hara;V. Bindokas;Chong C. Lee;Kenneth S. Polonsky;Graeme I. Bell;Richard J. Miller
中科院分区:
医学3区
文献类型:
--
作者:
S. Glaum;Manami Hara;V. Bindokas;Chong C. Lee;Kenneth S. Polonsky;Graeme I. Bell;Richard J. Miller

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我们研究了肥胖基因的产物瘦素对大鼠下丘脑脑片弓状核突触传递的影响。瘦素和神经肽Y(NPY)都能降低弓状核内诱发的兴奋性突触后电流。NPY还抑制GABA能抑制性突触后电流,而瘦素则无此作用。瘦素也降低了弓状神经元的输入电阻,这是伴随着激活的外向电流在去极化电位。瘦素调节急性分离的弓状神经元中的Ca 2+信号。在某些细胞中,由50 mM K+产生的细胞内钙浓度升高降低,而在其他细胞中则增加。然而,瘦素对突触传递没有影响,对含有突变瘦素受体的Zucker肥胖大鼠下丘脑中的Ca2+信号传导几乎没有影响。另一方面,NPY在Zucker瘦和肥胖大鼠中表现出突触调节作用。这些数据表明,瘦素可以在弓状核产生快速的突触调节作用,这可能有助于其对食物摄入的影响。
We examined the effects of leptin, the product of the obese gene, on synaptic transmission in the arcuate nucleus in rat hypothalamic slices. Both leptin and neuropeptide Y (NPY) reduced the evoked glutamatergic excitatory postsynaptic current in the arcuate nucleus. NPY also depressed the GABAergic inhibitory postsynaptic current, although leptin had no effect. Leptin also decreased the input resistance of arcuate neurons, and this was accompanied by the activation of an outward current at depolarized potentials. Leptin modulated Ca2+ signals in acutely isolated arcuate neurons. In some cells, the intracellular calcium concentration rise produced by 50 mM K+ was decreased, whereas in others it was increased. However, leptin produced no effects on synaptic transmission and little or no effect on Ca2+ signaling in the hypothalamus of Zucker fatty rats that contain mutated leptin receptors. On the other hand, NPY exhibited synaptic modulatory effects in Zucker lean and fatty rats. These data suggest that leptin can produce rapid synaptic modulatory effects in the arcuate nucleus, which may contribute to its effects on food intake.