Trophic action of leptin on hypothalamic neurons that regulate feeding
Trophic action of leptin on hypothalamic neurons that regulate feeding
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DOI：
10.1126/science.1095004
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发表时间：
2004-04-02
期刊：
影响因子：
56.9
通讯作者：
Simerly, RB
中科院分区：
文献类型：
--
作者：
Bouret, SG;Draper, SJ;Simerly, RB
在成年哺乳动物中，脂肪细胞衍生的激素瘦素通过调节下丘脑弓状核(ARH)神经元的活动来作用于大脑，以减少摄食量。在这里，我们报告了瘦素缺乏(Lep(Ob)/Lep(Ob))小鼠ARH的神经投射通路被永久性破坏，成年后的瘦素治疗不能逆转这些神经解剖缺陷。然而，用外源性瘦素治疗Lep(Ob)/Lep(Ob)新生儿可以挽救ARH投射的发育，并且瘦素在体外促进ARH神经元的突起生长。这些结果表明，瘦素在下丘脑的发育过程中起着神经营养作用，并且这种活动仅限于在成人瘦素对食物摄入量进行急性调节之前的新生儿关键期。
In adult mammals, the adipocyte-derived hormone leptin acts on the brain to reduce food intake by regulating the activity of neurons in the arcuate nucleus of the hypothalamus (ARH). Here, we report that neural projection pathways from the ARH are permanently disrupted in leptin-deficient (Lep(ob)/Lep(ob)) mice and leptin treatment in adulthood does not reverse these neuroanatomical defects. However, treatment of Lep(ob)/Lep(ob) neonates with exogenous leptin rescues the development of ARH projections, and leptin promotes neurite outgrowth from ARH neurons in vitro. These results suggest that leptin plays a neurotrophic role during the development of the hypothalamus and that this activity is restricted to a neonatal critical period that precedes leptin's acute regulation of food intake in adults.