Integration of stress and leptin signaling by CART producing neurons in the rodent midbrain centrally projecting Edinger-Westphal nucleus.
Integration of stress and leptin signaling by CART producing neurons in the rodent midbrain centrally projecting Edinger-Westphal nucleus.
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DOI：
10.3389/fnana.2014.00008
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发表时间：
2014
影响因子：
2.9
通讯作者：
Kozicz T
中科院分区：
文献类型：
--
作者：
Xu L;Janssen D;van der Knaap N;Roubos EW;Leshan RL;Myers MG Jr;Gaszner B;Kozicz T
瘦素靶向大脑以调节摄食、神经内分泌功能和代谢。瘦素受体存在于控制能量代谢的下丘脑中心以及中央投射的Edinger-Westphal核（EWcp）中，该区域涉及应激反应和应激相关行为的各个方面。我们假设可卡因和安非他明调节转录（CART）产生EWcp神经元的应激反应将取决于动物的能量状态。为了验证这一假设，我们研究了能量状态的变化（模拟低，正常和高瘦素水平，这是通过24小时禁食，正常的食物和瘦素注射，分别实现）对CART神经元的反应在EWCP的大鼠进行或不进行急性束缚应激的影响。我们的数据表明，单独的瘦素治疗显着增加CART mRNA的表达在大鼠EWcp和瘦素受体缺陷（db/db）小鼠，CART产生的神经元在这个核的数量减少。提示瘦素在非应激条件下对EWcp中CART的产生具有刺激作用。然而，在应激条件下，瘦素钝化应激诱导的EWcp神经元的激活，并降低其CART mRNA的表达。有趣的是，禁食并不影响EWcp神经元的应激诱导激活，特别是EWcp-CART神经元不被激活。这些结果表明，EWcp的应激反应在一定程度上取决于动物的能量状态，这一机制可能有助于更好地理解肥胖和应激之间复杂的相互作用。
Leptin targets the brain to regulate feeding, neuroendocrine function and metabolism. The leptin receptor is present in hypothalamic centers controlling energy metabolism as well as in the centrally projecting Edinger–Westphal nucleus (EWcp), a region implicated in the stress response and in various aspects of stress-related behaviors. We hypothesized that the stress response by cocaine- and amphetamine-regulated transcript (CART)-producing EWcp-neurons would depend on the animal’s energy state. To test this hypothesis, we investigated the effects of changes in energy state (mimicked by low, normal and high leptin levels, which were achieved by 24 h fasting, normal chow and leptin injection, respectively) on the response of CART neurons in the EWcp of rats subjected or not to acute restraint stress. Our data show that leptin treatment alone significantly increases CART mRNA expression in the rat EWcp and that in leptin receptor deficient (db/db) mice, the number of CART producing neurons in this nucleus is reduced. This suggests that leptin has a stimulatory effect on the production of CART in the EWcp under non-stressed condition. Under stressed condition, however, leptin blunts stress-induced activation of EWcp neurons and decreases their CART mRNA expression. Interestingly, fasting, does not influence the stress-induced activation of EWcp-neurons, and specifically EWcp-CART neurons are not activated. These results suggest that the stress response by the EWcp depends to some degree on the animal’s energy state, a mechanism that may contribute to a better understanding of the complex interplay between obesity and stress.
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影响因子：
4.8
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