Actions and Consequences of Insulin in the Striatum.
Actions and Consequences of Insulin in the Striatum.
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DOI：
10.3390/biom13030518
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发表时间：
2023-03-11
期刊：
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
胰岛素穿过血脑屏障从外周进入大脑。在大脑中，胰岛素在下丘脑以及中脑的中边缘多巴胺神经元水平上已经确定了作用。值得注意的是，胰岛素也在纹状体中起作用，纹状体中有大量的胰岛素受体（InsRs）表达。这些受体存在于中间神经元和纹状体突起神经元，以及神经胶质细胞和多巴胺轴突上。纹状体中胰岛素升高的一个显著功能后果是促进刺激多巴胺释放的增加。多巴胺释放的增加涉及到胆碱能中间神经元上的insr，并且需要激活多巴胺轴突上的尼古丁乙酰胆碱受体。与这种多巴胺增强作用相反，胰岛素也通过胰岛素在多巴胺轴突上的insr的作用增加多巴胺摄取。胰岛素也作用于其他纹状体细胞，包括纹状体投射神经元和星形胶质细胞，它们也影响多巴胺能传递和纹状体功能。将这些细胞发现与行为联系起来，纹状体胰岛素信号是味觉-营养学习发展所必需的，暗示胰岛素是大脑中的奖励信号。在这篇综述中，我们讨论了胰岛素在纹状体中的这些和其他作用，包括它们如何受到饮食和其他生理状态的影响。
Insulin crosses the blood–brain barrier to enter the brain from the periphery. In the brain, insulin has well-established actions in the hypothalamus, as well as at the level of mesolimbic dopamine neurons in the midbrain. Notably, insulin also acts in the striatum, which shows abundant expression of insulin receptors (InsRs) throughout. These receptors are found on interneurons and striatal projections neurons, as well as on glial cells and dopamine axons. A striking functional consequence of insulin elevation in the striatum is promoting an increase in stimulated dopamine release. This boosting of dopamine release involves InsRs on cholinergic interneurons, and requires activation of nicotinic acetylcholine receptors on dopamine axons. Opposing this dopamine-enhancing effect, insulin also increases dopamine uptake through the action of insulin at InsRs on dopamine axons. Insulin acts on other striatal cells as well, including striatal projection neurons and astrocytes that also influence dopaminergic transmission and striatal function. Linking these cellular findings to behavior, striatal insulin signaling is required for the development of flavor–nutrient learning, implicating insulin as a reward signal in the brain. In this review, we discuss these and other actions of insulin in the striatum, including how they are influenced by diet and other physiological states.
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