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中枢去甲肾上腺素能系统在神经发育障碍中的作用:实验与临床证据的融合。

The Central Noradrenergic System in Neurodevelopmental Disorders: Merging Experimental and Clinical Evidence.

机构信息

Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, 56126 Pisa, Italy.

Department of Developmental Neuroscience, IRCCS Fondazione Stella Maris, 56128 Pisa, Italy.

出版信息

Int J Mol Sci. 2023 Mar 18;24(6):5805. doi: 10.3390/ijms24065805.

Abstract

The aim of this article is to highlight the potential role of the locus-coeruleus-noradrenergic (LC-NA) system in neurodevelopmental disorders (NdDs). The LC is the main brain noradrenergic nucleus, key in the regulation of arousal, attention, and stress response, and its early maturation and sensitivity to perinatal damage make it an interesting target for translational research. Clinical data shows the involvement of the LC-NA system in several NdDs, suggesting a pathogenetic role in the development of such disorders. In this context, a new neuroimaging tool, LC Magnetic Resonance Imaging (MRI), has been developed to visualize the LC in vivo and assess its integrity, which could be a valuable tool for exploring morphological alterations in NdD in vivo in humans. New animal models may be used to test the contribution of the LC-NA system to the pathogenic pathways of NdD and to evaluate the efficacy of NA-targeting drugs. In this narrative review, we provide an overview of how the LC-NA system may represent a common pathophysiological and pathogenic mechanism in NdD and a reliable target for symptomatic and disease-modifying drugs. Further research is needed to fully understand the interplay between the LC-NA system and NdD.

摘要

本文旨在强调蓝斑-去甲肾上腺素能(LC-NA)系统在神经发育障碍(NdD)中的潜在作用。LC 是大脑主要的去甲肾上腺素能核团,对觉醒、注意力和应激反应的调节至关重要,其早期成熟和对围产期损伤的敏感性使其成为转化研究的有趣目标。临床数据显示,LC-NA 系统参与了多种 NdD,提示其在这些疾病的发展中具有发病机制作用。在此背景下,一种新的神经影像学工具——LC 磁共振成像(MRI)已被开发出来,用于在体内可视化 LC 并评估其完整性,这可能是探索人类体内 NdD 形态改变的有价值工具。新的动物模型可用于测试 LC-NA 系统对 NdD 发病途径的贡献,并评估针对 NA 的药物的疗效。在这篇叙述性综述中,我们概述了 LC-NA 系统如何可能代表 NdD 中的共同病理生理和发病机制,以及作为对症和疾病修饰药物的可靠靶点。需要进一步的研究来充分了解 LC-NA 系统与 NdD 之间的相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d405/10055776/bdd33edf5a0f/ijms-24-05805-g001.jpg

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