Histamine, Neuroinflammation and Neurodevelopment: A Review.
Histamine, Neuroinflammation and Neurodevelopment: A Review.
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DOI：
10.3389/fnins.2021.680214
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发表时间：
2021
影响因子：
4.3
通讯作者：
Ellender T
中科院分区：
文献类型：
--
作者：
Carthy E;Ellender T
生物胺，组胺，已被证明对炎症过程以及大脑中神经元和突触的特性进行关键调节，并与神经发育障碍的出现有关。事实上，这种神经调节剂合成的减少与多发性抽动症和强迫症有关，有证据表明，这可能是通过发育过程中皮质纹状体回路的中断而实现的。此外，神经炎症与大脑发育的改变有关，例如，影响突触可塑性和突触形成，而且有迹象表明，组胺缺乏可能使发育中的大脑更容易受到促炎侮辱。虽然大多数研究都集中在组胺的神经元来源上，但尚不清楚其他(非神经元)来源的组胺，例如肥大细胞和其他来源的组胺，可以在多大程度上影响大脑发育。已经开始在体外探索这一点的为数不多的研究表明，非神经元释放的组胺和其他预形成的介质可以影响小胶质细胞介导的神经炎症，从而影响大脑发育。在这篇综述中，我们将总结关于组胺的非神经性来源的领域的状况，以及它对神经炎症和神经发育的影响，这些神经回路是神经发育障碍的基础。我们还将讨论组胺受体调节剂在临床前和临床研究中是否在治疗神经发育障碍方面有效。这可能代表着未来研究的一个重要领域，因为来自神经元和非神经元来源的组胺的早期调节可能为这些疾病提供新的治疗靶点。
The biogenic amine, histamine, has been shown to critically modulate inflammatory processes as well as the properties of neurons and synapses in the brain, and is also implicated in the emergence of neurodevelopmental disorders. Indeed, a reduction in the synthesis of this neuromodulator has been associated with the disorders Tourette’s syndrome and obsessive-compulsive disorder, with evidence that this may be through the disruption of the corticostriatal circuitry during development. Furthermore, neuroinflammation has been associated with alterations in brain development, e.g., impacting synaptic plasticity and synaptogenesis, and there are suggestions that histamine deficiency may leave the developing brain more vulnerable to proinflammatory insults. While most studies have focused on neuronal sources of histamine it remains unclear to what extent other (non-neuronal) sources of histamine, e.g., from mast cells and other sources, can impact brain development. The few studies that have started exploring this in vitro, and more limited in vivo, would indicate that non-neuronal released histamine and other preformed mediators can influence microglial-mediated neuroinflammation which can impact brain development. In this Review we will summarize the state of the field with regard to non-neuronal sources of histamine and its impact on both neuroinflammation and brain development in key neural circuits that underpin neurodevelopmental disorders. We will also discuss whether histamine receptor modulators have been efficacious in the treatment of neurodevelopmental disorders in both preclinical and clinical studies. This could represent an important area of future research as early modulation of histamine from neuronal as well as non-neuronal sources may provide novel therapeutic targets in these disorders.
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影响因子：
4.7
作者：
Bolam JP;Ellender TJ
通讯作者：
Ellender TJ
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