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连接发育性脑损伤的神经生物学:神经元树突分支作为功能障碍的调节剂和潜在治疗靶点。

Connecting the Neurobiology of Developmental Brain Injury: Neuronal Arborisation as a Regulator of Dysfunction and Potential Therapeutic Target.

机构信息

Department of Comparative Biomedical Sciences, Royal Veterinary College, London NW1 0TU, UK.

出版信息

Int J Mol Sci. 2021 Jul 30;22(15):8220. doi: 10.3390/ijms22158220.

Abstract

Neurodevelopmental disorders can derive from a complex combination of genetic variation and environmental pressures on key developmental processes. Despite this complex aetiology, and the equally complex array of syndromes and conditions diagnosed under the heading of neurodevelopmental disorder, there are parallels in the neuropathology of these conditions that suggest overlapping mechanisms of cellular injury and dysfunction. Neuronal arborisation is a process of dendrite and axon extension that is essential for the connectivity between neurons that underlies normal brain function. Disrupted arborisation and synapse formation are commonly reported in neurodevelopmental disorders. Here, we summarise the evidence for disrupted neuronal arborisation in these conditions, focusing primarily on the cortex and hippocampus. In addition, we explore the developmentally specific mechanisms by which neuronal arborisation is regulated. Finally, we discuss key regulators of neuronal arborisation that could link to neurodevelopmental disease and the potential for pharmacological modification of arborisation and the formation of synaptic connections that may provide therapeutic benefit in the future.

摘要

神经发育障碍可能源于遗传变异和关键发育过程中环境压力的复杂组合。尽管病因复杂,在神经发育障碍这一标题下诊断的综合征和病症也同样复杂,但这些病症的神经病理学存在相似之处,表明存在细胞损伤和功能障碍的重叠机制。神经元树突分支是一个树突和轴突延伸的过程,对于支持正常大脑功能的神经元之间的连接至关重要。在神经发育障碍中,树突分支和突触形成的破坏经常被报道。在这里,我们总结了这些病症中神经元树突分支破坏的证据,主要集中在皮层和海马体上。此外,我们还探讨了神经元树突分支受到调控的发育特定机制。最后,我们讨论了可能与神经发育性疾病相关的神经元树突分支的关键调节因子,以及对树突分支和突触连接形成进行药理学修饰的潜力,这可能为未来提供治疗益处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e5e/8348801/dbb58accada2/ijms-22-08220-g001.jpg

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