Induction of brain-derived neurotrophic factor by leptin in the ventromedial hypothalamus
Induction of brain-derived neurotrophic factor by leptin in the ventromedial hypothalamus
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DOI：
10.1016/j.neuroscience.2005.12.066
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发表时间：
2006-01-01
期刊：
影响因子：
3.3
通讯作者：
Senba, E.
中科院分区：
文献类型：
--
作者：
Komori, T.;Morikawa, Y.;Senba, E.
瘦素是一种脂肪细胞源性激素，通过调节下丘脑中的食欲和食欲因子来减少食物摄入。虽然脑源性神经营养因子是下丘脑中重要的促凋亡因子，但关于瘦素对下丘脑中脑源性神经营养因子表达的调节知之甚少。在本研究中，我们研究了瘦素对下丘脑脑源性神经营养因子表达的影响。静脉注射瘦素（10 μ g/g）导致脑源性神经营养因子mRNA的表达增加，这是在下丘脑腹内侧核的背内侧部分观察到的。在磷酸化的信号转导子和转录激活子3阳性神经元中检测到脑源性神经营养因子mRNA的表达增加，表明瘦素诱导下丘脑腹内侧核背内侧部神经元中的脑源性神经营养因子表达。此外，瘦素注射小鼠下丘脑腹内侧核脑源性神经营养因子的表达在蛋白水平上增加。有趣的是，脑源性神经营养因子阳性纤维也增加了腹内侧下丘脑核和背内侧下丘脑核的瘦素注射小鼠，这是在密切并列酪氨酸激酶受体B免疫反应阳性神经元和共定位与突触素，突触前末梢的标记。提示瘦素可诱导下丘脑腹内侧核背内侧部脑源性神经营养因子的表达，脑源性神经营养因子可能通过激活下丘脑腹内侧核和背内侧核的酪氨酸激酶受体B发挥促凋亡作用。(c)2006由Elsevier Ltd代表IBRO出版。
Leptin, an adipocyte-derived hormone, reduces food intake by regulating orexigenic and anorexigenic factors in the hypothalamus. Although brain-derived neurotrophic factor is an important anorexigenic factor in the hypothalamus, little is known about the regulation of brain-derived neurotrophic factor expression by leptin in the hypothalamus. In the present study, we examined the effect of leptin on the expression of brain-derived neurotrophic factor in the hypothalamus. I.v. administration of leptin (10 mu g/g) led to the increase in the expression of brain-derived neurotrophic factor mRNA, which was observed in the dorsomedial part of the ventromedial hypothalamic nucleus. The increased expression of brain-derived neurotrophic factor mRNA was detected in phosphorylated signal transducer and activator of transcription 3-positive neurons, suggesting that leptin induced brain-derived neurotrophic factor expression in neurons of the dorsomedial part of the ventromedial hypothalamic nucleus. In addition, the expression of brain-derived neurotrophic factor was increased at the protein level in the ventromedial hypothalamic nucleus of leptin-injected mice. Interestingly, brain-derived neurotrophic factor-positive fibers also increased in the ventromedial hypothalamic nucleus and dorsomedial hypothalamic nucleus of leptin-injected mice, which were in close apposition to tyrosine kinase receptor B-immunoreactive neurons and colocalized with synaptophysin, a marker of presynaptic terminals. These results suggest that leptin induces brain-derived neurotrophic factor expression in the dorsomedial part of the ventromedial hypothalamic nucleus and brain-derived neurotrophic factor may exert as anorexigenic factors possibly through the activation of tyrosine kinase receptor B in the ventromedial hypothalamic nucleus and dorsomedial hypothalamic nucleus. (c) 2006 Published by Elsevier Ltd on behalf of IBRO.