Regulation of neurological and neuropsychiatric phenotypes by locus coeruleus-derived galanin.
Regulation of neurological and neuropsychiatric phenotypes by locus coeruleus-derived galanin.
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DOI：
10.1016/j.brainres.2015.11.025
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发表时间：
2016-06-15
期刊：
影响因子：
2.9
通讯作者：
Holmes PV
中科院分区：
文献类型：
--
作者：
Weinshenker D;Holmes PV
数十年的研究证实，去甲肾上腺素能蓝斑 (LC) 神经元对于唤醒、注意力、动机和压力反应至关重要。虽然大多数关于 LC 传输的研究都集中在去甲肾上腺素 (NE) 上，但肾上腺素信号传导不能解释 LC 激活的所有后果。甘丙肽与 NE 共存于绝大多数 LC 神经元中，但鉴于我们对 LC 系统的深入了解，这种神经肽的精确功能已被证明令人惊讶地难以捉摸。为了阐明甘丙肽对 LC 生理学的贡献，我们从神经解剖学的角度简要总结了驱动 LC 活动的刺激的本质。我们继续描述甘丙肽最有可能对行为产生影响的 LC 途径，重点关注成瘾、抑郁、癫痫、压力和阿尔茨海默病。我们提出了一种模型，其中 LC 衍生的甘丙肽具有两种不同的功能：作为神经调节剂，主要通过甘丙肽 1 受体 (GAL1) 发挥作用；作为营养因子，主要通过甘丙肽受体 2 (GAL2) 发挥作用。最后，我们讨论了如何利用神经肽检测、光遗传学和化学遗传学以及甘丙肽受体药理学的最新进展来明确鉴定LC衍生的甘丙肽的作用。
Decades of research confirm that noradrenergic locus coeruleus (LC) neurons are essential for arousal, attention, motivation, and stress responses. While most studies on LC transmission focused unsurprisingly on norepinephrine (NE), adrenergic signaling cannot account for all the consequences of LC activation. Galanin coexists with NE in the vast majority of LC neurons, yet the precise function of this neuropeptide has proved to be surprisingly elusive given our solid understanding of the LC system. To elucidate the contribution of galanin to LC physiology, here we briefly summarize the nature of stimuli that drive LC activity from a neuroanatomical perspective. We go on to describe the LC pathways in which galanin most likely exerts its effects on behavior, with a focus on addiction, depression, epilepsy, stress, and Alzheimer’s disease. We propose a model in which LC-derived galanin has two distinct functions: as a neuromodulator, primarily acting via the galanin 1 receptor (GAL1), and as a trophic factor, primarily acting via galanin receptor 2 (GAL2). Finally, we discuss how the recent advances in neuropeptide detection, optogenetics and chemical genetics, and galanin receptor pharmacology can be harnessed to identify the roles of LC-derived galanin definitively.