Differential acute and chronic effects of leptin on hypothalamic astrocyte morphology and synaptic protein levels.
Differential acute and chronic effects of leptin on hypothalamic astrocyte morphology and synaptic protein levels.
复制标题
DOI：
10.1210/en.2010-1252
复制
发表时间：
2011-05
期刊：
影响因子：
4.8
通讯作者：
Chowen JA
中科院分区：
文献类型：
--
作者：
García-Cáceres C;Fuente-Martín E;Burgos-Ramos E;Granado M;Frago LM;Barrios V;Horvath T;Argente J;Chowen JA
瘦素对下丘脑的星形胶质细胞结构蛋白和突触蛋白产生相反的影响，与急性和慢性暴露的作用相反。星形胶质细胞参与神经内分泌功能的部分途径是通过调节下丘脑的突触输入密度。事实上，神经元的神经胶质鞘被特定的激素改变，从而决定了突触输入的神经元膜空间的可用性，这种可塑性的丧失可能参与了病理过程。瘦素调节下丘脑的突触输入，但星形胶质细胞是否参与这一作用尚不清楚。在这里，我们报道了长期给予瘦素(侧脑室，2wk)可诱导星形胶质细胞结构蛋白，如胶质纤维酸性蛋白(GFAP)和波形蛋白，并改变星形胶质细胞的形态，这些改变与突触蛋白密度的改变成反比。在成年雄性大鼠中也观察到了类似的变化，这些大鼠由于新生儿营养过剩(营养过剩：每窝4只幼鼠与对照组：12只幼崽/窝)体重增加和循环瘦素水平增加。然而，急性瘦素治疗后1h，下丘脑GFAP水平降低，突触蛋白水平升高，而对波形蛋白无影响。在原代培养的下丘脑星形胶质细胞中，瘦素也在1小时降低GFAP的水平，并在24小时诱导，这表明瘦素可能有直接作用。因此，瘦素可能影响新陈代谢的一个机制是通过改变下丘脑星形胶质细胞的形态，这反过来又可以改变下丘脑神经元的突触输入。此外，对急性和慢性瘦素暴露的反应是相反的，增加了对慢性瘦素暴露反应中胶质细胞激活增加的可能性，可能涉及中枢性瘦素抵抗。
Leptin induces inverse effects on astrocyte structural proteins and synaptic proteins in the hypothalamus, with opposite effects of acute and chronic exposure. Astrocytes participate in neuroendocrine functions partially through modulation of synaptic input density in the hypothalamus. Indeed, glial ensheathing of neurons is modified by specific hormones, thus determining the availability of neuronal membrane space for synaptic inputs, with the loss of this plasticity possibly being involved in pathological processes. Leptin modulates synaptic inputs in the hypothalamus, but whether astrocytes participate in this action is unknown. Here we report that astrocyte structural proteins, such as glial fibrillary acidic protein (GFAP) and vimentin, are induced and astrocyte morphology modified by chronic leptin administration (intracerebroventricular, 2 wk), with these changes being inversely related to modifications in synaptic protein densities. Similar changes in glial structural proteins were observed in adult male rats that had increased body weight and circulating leptin levels due to neonatal overnutrition (overnutrition: four pups/litter vs. control: 12 pups/litter). However, acute leptin treatment reduced hypothalamic GFAP levels and induced synaptic protein levels 1 h after administration, with no effect on vimentin. In primary hypothalamic astrocyte cultures leptin also reduced GFAP levels at 1 h, with an induction at 24 h, indicating a possible direct effect of leptin. Hence, one mechanism by which leptin may affect metabolism is by modifying hypothalamic astrocyte morphology, which in turn could alter synaptic inputs to hypothalamic neurons. Furthermore, the responses to acute and chronic leptin exposure are inverse, raising the possibility that increased glial activation in response to chronic leptin exposure could be involved in central leptin resistance.
登录
查看更多内容
影响因子：
4.1
作者：
Guan, XM;Hess, JF;vanderPloeg, LHT
通讯作者：
vanderPloeg, LHT
影响因子：
56.9
作者：
Bouret, SG;Draper, SJ;Simerly, RB
通讯作者：
Simerly, RB
影响因子：
4.8
作者：
McGregor, GP;Desaga, JF;Lang, RE
通讯作者：
Lang, RE
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
2.4
作者：
Mirshamsi S;Laidlaw HA;Ning K;Anderson E;Burgess LA;Gray A;Sutherland C;Ashford ML
通讯作者：
Ashford ML