GLP-1 action in the mouse bed nucleus of the stria terminalis.
GLP-1 action in the mouse bed nucleus of the stria terminalis.
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DOI：
10.1016/j.neuropharm.2017.12.007
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发表时间：
2018-03-15
影响因子：
4.7
通讯作者：
Trapp S
中科院分区：
文献类型：
--
作者：
Williams DL;Lilly NA;Edwards IJ;Yao P;Richards JE;Trapp S
胰高血糖素样肽-1（GLP-1）注射到大脑中会减少食物摄入。类似地，后脑中合成GLP-1的前胰高血糖素原（PPG）细胞的活化减少食物摄入。然而，目前还不清楚这种情况是否是因为饱腹感、恶心、奖励减少，甚至是压力。在这里，我们探讨的作用，床核的终纹（BNST），一个地区参与摄食控制以及应激反应，在GLP-1的反应。使用表达cre的小鼠，我们可视化了NTS PPG神经元和表达GLP-1 R的BNST细胞与AAV驱动的视紫红质-YFP表达的投射。在BNST中，腹侧区有许多曲张的YFP+ PPG轴突，背侧区较少。在GLP-1 R神经元中表达RFP的小鼠在整个BNST中具有RFP+细胞，其中背侧部分的密度最高，表明PPG神经元衍生的GLP-1在BNST中起作用。事实上，将GLP-1注射到BNST中减少了黑暗期期间的食物摄入，而注射GLP-1受体拮抗剂Ex 9增加了进食。BNST特异性GLP-1诱导的食物抑制在高脂肪（HF，60%）饮食的小鼠中不太有效，并且Ex 9没有作用。束缚应激诱导的食欲减退通过BNST Ex 9处理减弱，进一步支持内源性脑GLP-1的作用。最后，RFP+ BNST神经元的全细胞膜片钳记录表明，GLP-1引起去极化或超极化可逆反应，其极性与多巴胺相反。我们的数据支持BNST GLP-1 R在摄食中的生理作用，并表明该细胞核中对GLP-1的复杂细胞反应。NTS PPG神经元强烈投射到BNST。在BNST中起作用的外源性或内源性GLP-1有效地减少食物摄入。在BNST中，GLP-1受体阻断剂可减轻应激诱导的摄食量减少。在BNST内，GLP-1激发兴奋性和抑制性电反应。GLP-1可能作用于BNST的促食欲和促食欲传出通路。
Glucagon-like peptide-1 (GLP-1) injected into the brain reduces food intake. Similarly, activation of preproglucagon (PPG) cells in the hindbrain which synthesize GLP-1, reduces food intake. However, it is far from clear whether this happens because of satiety, nausea, reduced reward, or even stress. Here we explore the role of the bed nucleus of the stria terminalis (BNST), an area involved in feeding control as well as stress responses, in GLP-1 responses. Using cre-expressing mice we visualized projections of NTS PPG neurons and GLP-1R-expressing BNST cells with AAV-driven Channelrhodopsin-YFP expression. The BNST displayed many varicose YFP+ PPG axons in the ventral and less in the dorsal regions. Mice which express RFP in GLP-1R neurons had RFP+ cells throughout the BNST with the highest density in the dorsal part, suggesting that PPG neuron-derived GLP-1 acts in the BNST. Indeed, injection of GLP-1 into the BNST reduced chow intake during the dark phase, whereas injection of the GLP-1 receptor antagonist Ex9 increased feeding. BNST-specific GLP-1-induced food suppression was less effective in mice on high fat (HF, 60%) diet, and Ex9 had no effect. Restraint stress-induced hypophagia was attenuated by BNST Ex9 treatment, further supporting a role for endogenous brain GLP-1. Finally, whole-cell patch clamp recordings of RFP+ BNST neurons demonstrated that GLP-1 elicited either a depolarizing or hyperpolarizing reversible response that was of opposite polarity to that under dopamine. Our data support a physiological role for BNST GLP-1R in feeding, and suggest complex cellular responses to GLP-1 in this nucleus. NTS PPG neurons project strongly to the BNST. Exogenous or endogenous GLP-1 acting in the BNST potently reduces food intake. Stress-induced hypophagia is attenuated by GLP-1 receptor blockade in the BNST. Within the BNST, GLP-1 elicits both excitatory and inhibitory electrical responses. GLP-1 likely acts on both orexigenic and anorexigenic efferent pathways from the BNST.
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DOI：
10.1523/jneurosci.3262-11.2011
发表时间：
2011-10-12
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Dossat AM;Lilly N;Kay K;Williams DL
通讯作者：
Williams DL
影响因子：
3.3
作者：
Llewellyn-Smith, I. J.;Reimann, F.;Gribble, F. M.;Trapp, S.
通讯作者：
Trapp, S.
下丘脑胰高血糖素样肽1受体足够，但对于调节小鼠的能量平衡和葡萄糖稳态不需要。
影响因子：
7.7
作者：
Burmeister MA;Ayala JE;Smouse H;Landivar-Rocha A;Brown JD;Drucker DJ;Stoffers DA;Sandoval DA;Seeley RJ;Ayala JE
通讯作者：
Ayala JE
影响因子：
5.3
作者：
Maniscalco, James W.;Zheng, Huiyuan;Rinaman, Linda
通讯作者：
Rinaman, Linda
影响因子：
2.5
作者：
Dong, HW;Swanson, LW
通讯作者：
Swanson, LW