Imaging the endocannabinoid signaling system.

Imaging the endocannabinoid signaling system.
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内源性大麻素信号系统成像。

DOI:
10.1016/j.jneumeth.2021.109451
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发表时间:
2022-02-01
影响因子:
3
通讯作者:
Soltesz I
Soltesz I
中科院分区:
医学4区
文献类型:
--
作者:
Dudok B;Soltesz I

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内源性大麻素(eCB)系统是哺乳动物大脑中最广泛的神经调节系统之一,在从发育到突触可塑性等功能中发挥着多方面的作用。内源性大麻素是根据膜脂前体的需要合成的,主要作用于单一 G 蛋白偶联受体类型 CB1,以执行多种功能。尽管 eCB 系统在健康大脑功能和疾病中都很重要,但 eCB 信号转导的极其重要的细节仍然未知。 eCB 如何从膜中释放、这些脂质分子如何在细胞之间运输以及如何控制其受体的分布,仍然是个谜。光学显微镜方法和生物传感器工程的最新进展可能为研究 eCB 信号传导开辟新途径。我们总结了超分辨率显微镜的应用,使用单分子定位来揭示神经元轴突和轴突末端纳米级 CB1 分布的不同模式。我们回顾了使用量子点进行的单粒子跟踪研究,该研究允许可视化 CB1 轨迹。我们重点介绍荧光 eCB 生物传感器的最新发展,该传感器揭示了活细胞和活体动物中 eCB 的时空特异性释放。最后,我们讨论了方法开发可能有助于促进对 eCB 信号传输的精确理解的未来方向。
The endocannabinoid (eCB) system is one of the most widespread neuromodulatory systems in the mammalian brain, with a multifaceted role in functions ranging from development to synaptic plasticity. Endocannabinoids are synthesized on demand from membrane lipid precursors, and act primarily on a single G-protein coupled receptor type, CB1, to carry out diverse functions. Despite the importance of the eCB system both in healthy brain function and in disease, critically important details of eCB signaling remained unknown. How eCBs are released from the membrane, how these lipid molecules are transported between cells, and how the distribution of their receptors is controlled, remained elusive. Recent advances in optical microscopy methods and biosensor engineering may open up new avenues for studying eCB signaling. We summarize applications of superresolution microscopy using single molecule localization to reveal distinct patterns of nanoscale CB1distribution in neuronal axons and axon terminals. We review single particle tracking studies using quantum dots that allowed visualizing CB1trajectories. We highlight the recent development of fluorescent eCB biosensors, that revealed spatiotemporally specific eCB release in live cells and live animals. Finally, we discuss future directions where method development may help to advance a precise understanding of eCB signaling.
用于体内内源性大麻素动态时空分辨成像的荧光传感器
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