Ghrelin signaling in the ventral hippocampus stimulates learned and motivational aspects of feeding via PI3K-Akt signaling.
Ghrelin signaling in the ventral hippocampus stimulates learned and motivational aspects of feeding via PI3K-Akt signaling.
复制标题
腹侧海马中的生长素素信号传导通过PI3K-AKT信号传导刺激了喂养的学习和动机方面。
DOI：
10.1016/j.biopsych.2012.07.002
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发表时间：
2013-05-01
影响因子：
10.6
通讯作者：
Grill, Harvey J.
中科院分区：
文献类型：
--
作者：
Kanoski, Scott E.;Fortin, Samantha M.;Ricks, Katie M.;Grill, Harvey J.
胃源性激素ghrelin通过其受体（GHSR 1A）的CNS信号传导驱动与食物奖励和食物寻找相关的高阶进食过程。介导这些效应的特定核仅部分了解。在这里，我们使用大鼠模型，以检查是否在海马腹侧亚区（VHPC），最近的兴趣在能量平衡控制的大脑基板的ghrelin信号，影响学习和动机方面的喂养行为。VHPC生长素释放肽管理的影响进行了检查喂养相关的行为模式，包括膳食模式分析，操作杠杆压蔗糖，和条件刺激诱导的喂养。使用免疫印迹分析和行为药理学评估由VHPC GHSR 1A激活刺激的细胞内信号传导和下游神经元通路。胃饥饿素传递到VHPC，但不是背海马，增加食物摄入量主要是通过增加用餐频率。内VHPC生长素释放肽交付也增加了愿意工作的蔗糖和增加自发的膳食开始后，在非剥夺大鼠的条件刺激，以前的信号膳食访问时，大鼠的食物限制。VHPC生长素释放肽的食物摄取增强作用通过共同施用磷酸肌醇3-激酶（PI 3 K）抑制剂（LY 294002）来阻断。免疫印迹分析为VHPC中生长素释放肽激活PI 3 K-Akt信号传导提供了补充支持，并揭示这种激活随着高脂肪饮食消耗而减弱。其他免疫印迹结果表明，VHPC GHSR 1A信号激活了丘脑核中的下游多巴胺能活性。这些发现阐明了新的神经元和行为机制介导饥饿素的调制认知方面的喂养控制。
The stomach-derived hormone ghrelin drives higher-order feeding processes related to food reward and food seeking via CNS signaling at its receptor (GHSR1A). The specific nuclei mediating these effects are only partially understood. Here, we use a rat model to examine whether ghrelin signaling in the ventral subregion of the hippocampus (VHPC), a brain substrate of recent interest in energy balance control, affects learned and motivational aspects of feeding behavior. The effects of VHPC ghrelin administration were examined on feeding-relevant behavioral paradigms, including meal pattern analysis, operant lever pressing for sucrose, and conditioned stimulus-induced feeding. The intracellular signaling and downstream neuronal pathways stimulated by VHPC GHSR1A activation were assessed using immunoblot analysis and behavioral pharmacology. Ghrelin delivery to the VHPC, but not the dorsal hippocampus, increased food intake primarily by increasing meal frequency. Intra-VHPC ghrelin delivery also increased willingness to work for sucrose and increased spontaneous meal initiation in nondeprived rats following the presentation of a conditioned stimulus that previously signaled meal access when the rats were food restricted. The food intake enhancing effects of VHPC ghrelin were blocked by co-administration of a phosphoinositide 3-kinase (PI3K) inhibitor (LY294002). Immunoblot analyses provided complementary support for ghrelin activated PI3K-Akt signaling in the VHPC and revealed that this activation is blunted with high fat diet consumption. Other immunoblot results show that VHPC GHSR1A signaling activates downstream dopaminergic activity in the nucleus accumbens. These findings illuminate novel neuronal and behavioral mechanisms mediating ghrelin's modulation of cognitive aspects of feeding control.
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影响因子：
16.2
作者：
Fanselow, Michael S.;Dong, Hong-Wei
通讯作者：
Dong, Hong-Wei
影响因子：
2.9
作者：
Davidson, TL;Kanoski, SE;Jarrard, LE
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Jarrard, LE
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16.2
作者：
Cowley, MA;Smith, RG;Horvath, TL
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Horvath, TL
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作者：
Abizaid, Alfonso;Liu, Zhong-Wu;Horvath, Tamas L.
通讯作者：
Horvath, Tamas L.
影响因子：
3
作者：
Carlini, Valeria P.;Ghersi, Marisa;de Barioglio, Susana R.
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de Barioglio, Susana R.