TrkB receptor signaling in the nucleus tractus solitarius mediates the food intake-suppressive effects of hindbrain BDNF and leptin.
TrkB receptor signaling in the nucleus tractus solitarius mediates the food intake-suppressive effects of hindbrain BDNF and leptin.
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DOI：
10.1152/ajpendo.00025.2012
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发表时间：
2012-05
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影响因子：
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通讯作者：
A. Spaeth;S. Kanoski;M. R. Hayes;H. Grill
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文献类型：
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作者：
A. Spaeth;S. Kanoski;M. R. Hayes;H. Grill
脑源性神经营养因子（BDNF）和TrkB受体信号有助于中枢神经系统（CNS）控制能量平衡。本文研究了后脑BDNF/TrkB受体信号在能量平衡调节中的作用。后脑脑室BDNF通过减少总食物摄入量和膳食量以及增加核心温度来抑制体重。定位神经元介导的能量平衡的影响，后脑脑室递送BDNF，脑室阈下剂量直接传递到内侧孤束核（mNTS）。给予mNTS BDNF显著减少食物摄入，并且这种作用被预先给予高度选择性的Trk B受体拮抗剂{[N2-2-2-Oxoazepan-3-yl amino]carbonyl phenyl benzo（B）thiophene-2-carboxamide（ANA-12）}阻断，表明Trk B受体活化介导了后脑BDNF对食物摄入的作用。由于BDNF和瘦素都与黑皮质素信号相互作用以减少食物摄入，我们还研究了后脑瘦素的摄入抑制作用是否涉及后脑特异性BDNF/TrkB激活。脑内背侧迷走神经复合体的BDNF蛋白含量显着增加后脑瘦素传递。为了评估BDNF/TrkB受体信号传导是否在能量平衡的控制中在瘦素信号传导的下游起作用，将瘦素和ANA-12共同施用到mNTS中。TrkB受体拮抗剂的管理衰减瘦素的摄入抑制作用，表明mNTS TrkB受体激活有助于介导后脑瘦素的促肾上腺皮质激素生成作用。总的来说，这些结果表明，TrkB介导的信号在mNTS负调节食物摄入，并在一定程度上，摄入抑制作用的瘦素管理到NTS。
Brain-derived neurotrophic factor (BDNF) and TrkB receptor signaling contribute to the central nervous system (CNS) control of energy balance. The role of hindbrain BDNF/TrkB receptor signaling in energy balance regulation is examined here. Hindbrain ventricular BDNF suppressed body weight through reductions in overall food intake and meal size and by increasing core temperature. To localize the neurons mediating the energy balance effects of hindbrain ventricle-delivered BDNF, ventricle subthreshold doses were delivered directly to medial nucleus tractus solitarius (mNTS). mNTS BDNF administration reduced food intake significantly, and this effect was blocked by preadministration of a highly selective TrkB receptor antagonist {[N2-2-2-Oxoazepan-3-yl amino]carbonyl phenyl benzo (b)thiophene-2-carboxamide (ANA-12)}, suggesting that TrkB receptor activation mediates hindbrain BDNF's effect on food intake. Because both BDNF and leptin interact with melanocortin signaling to reduce food intake, we also examined whether the intake inhibitory effects of hindbrain leptin involve hindbrain-specific BDNF/TrkB activation. BDNF protein content within the dorsal vagal complex of the hindbrain was increased significantly by hindbrain leptin delivery. To assess if BDNF/TrkB receptor signaling acts downstream of leptin signaling in the control of energy balance, leptin and ANA-12 were coadministered into the mNTS. Administration of the TrkB receptor antagonist attenuated the intake-suppressive effects of leptin, suggesting that mNTS TrkB receptor activation contributes to the mediation of the anorexigenic effects of hindbrain leptin. Collectively, these results indicate that TrkB-mediated signaling in the mNTS negatively regulates food intake and, in part, the intake inhibitory effects of leptin administered into the NTS.