Amylin Acts in the Lateral Dorsal Tegmental Nucleus to Regulate Energy Balance Through Gamma-Aminobutyric Acid Signaling.
Amylin Acts in the Lateral Dorsal Tegmental Nucleus to Regulate Energy Balance Through Gamma-Aminobutyric Acid Signaling.
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DOI：
10.1016/j.biopsych.2016.12.028
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发表时间：
2017-12-01
影响因子：
10.6
通讯作者：
Hayes MR
中科院分区：
文献类型：
--
作者：
Reiner DJ;Mietlicki-Baase EG;Olivos DR;McGrath LE;Zimmer DJ;Koch-Laskowski K;Krawczyk J;Turner CA;Noble EE;Hahn JD;Schmidt HD;Kanoski SE;Hayes MR
胰腺和脑源性激素胰淀素促进负能量平衡，并作为一种有前途的肥胖治疗剂受到越来越多的关注。然而，介导胰淀素作用的神经生物学底物尚未完全表征。我们假设胰淀素作用于被盖背外侧核（LDTg），这是一个未充分研究的奖励和稳态进食信号的神经处理中心。我们使用免疫组化（IHC）和定量PCR分析，以检查大鼠LDTg组织中胰淀素受体复合物的表达。行为实验进行检查的机制胰淀素受体激活的低吞噬作用的LDTg。IHC和定量PCR分析显示胰淀素受体复合物在LDTg中的表达。激动剂鲑鱼降钙素对LDTg胰淀素受体的激活剂量依赖性地降低体重、食物摄入量和有动机的进食行为。急性药理学研究和长期腺相关病毒（AAV）敲低实验表明，LDTg胰淀素受体信号传导在生理上和潜在临床前与能量平衡控制相关。最后，IHC数据表明LDTg胰淀素受体在γ-氨基丁酸（GABA）能神经元上表达，行为结果表明，局部GABA受体信号传导介导LDTg胰淀素受体激活后的摄食不足。这些发现将LDTg鉴定为在介导胰淀素通过GABA受体信号传导对能量平衡的作用中具有治疗潜力的新型核。
The pancreatic- and brain-derived hormone amylin promotes negative energy balance and is receiving increasing attention as a promising obesity therapeutic. However, the neurobiological substrates mediating amylin’s effects are not fully characterized. We postulated that amylin acts in the lateral dorsal tegmental nucleus (LDTg), an understudied neural-processing hub for reward and homeostatic feeding signals. We used immunohistochemical (IHC) and quantitative PCR analyses to examine expression of the amylin receptor complex in rat LDTg tissue. Behavioral experiments were performed to examine the mechanisms underlying the hypophagic effects of amylin receptor activation in the LDTg. IHC and quantitative PCR analyses show expression of the amylin receptor complex in the LDTg. Activation of LDTg amylin receptors by the agonist salmon calcitonin dose-dependently reduces body weight, food intake, and motivated feeding behaviors. Acute pharmacological studies and longer-term adeno-associated viral (AAV)-knockdown experiments indicate that LDTg amylin receptor signaling is physiologically and potentially pre-clinically relevant for energy balance control. Finally, IHC data indicate that LDTg amylin receptors are expressed on gamma-aminobutyric acid (GABA)-ergic neurons and behavioral results suggest that local GABA receptor signaling mediates the hypophagia following LDTg amylin receptor activation. These findings identify the LDTg as a novel nucleus with therapeutic potential in mediating amylin’s effects on energy balance through GABA receptor signaling.
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影响因子：
7.6
作者：
Baisley, Sarah K.;Baldo, Brian A.
通讯作者：
Baldo, Brian A.
DOI：
10.1152/ajpregu.00462.2015
发表时间：
2016-02-15
影响因子：
2.8
作者：
Dunn-Meynell, Ambrose A.;Le Foll, Christelle;Levin, Barry E.
通讯作者：
Levin, Barry E.
影响因子：
4.9
作者：
Lutz, TA;Mollet, A;Scharrer, E
通讯作者：
Scharrer, E
影响因子：
3
作者：
Lutz, TA;Rossi, R;Scharrer, E
通讯作者：
Scharrer, E
影响因子：
4.7
作者：
Kanoski SE;Rupprecht LE;Fortin SM;De Jonghe BC;Hayes MR
通讯作者：
Hayes MR