Neuronal activity is the basis of information encoding and processing in the brain. During neuronal activation, intracellular ATP (adenosine triphosphate) is generated to meet the high-energy demands. Simultaneously, ATP is secreted, increasing the extracellular ATP concentration and acting as a homeostatic messenger that mediates cell–cell communication to prevent aberrant hyperexcitability of the nervous system. In addition to the confined release and fast synaptic signaling of classic neurotransmitters within synaptic clefts, ATP can be released by all brain cells, diffuses widely, and targets different types of purinergic receptors on neurons and glial cells, making it possible to orchestrate brain neuronal activity and participate in various physiological processes, such as sleep and wakefulness, learning and memory, and feeding. Dysregulation of extracellular ATP leads to a destabilizing effect on the neural network, as found in the etiopathology of many psychiatric diseases, including depression, anxiety, schizophrenia, and autism spectrum disorder. In this review, we summarize advances in the understanding of the mechanisms by which extracellular ATP serves as an intercellular signaling molecule to regulate neural activity, with a focus on how it maintains the homeostasis of neural networks. In particular, we also focus on neural activity issues that result from dysregulation of extracellular ATP and propose that aberrant levels of extracellular ATP may play a role in the etiopathology of some psychiatric diseases, highlighting the potential therapeutic targets of ATP signaling in the treatment of these psychiatric diseases. Finally, we suggest potential avenues to further elucidate the role of extracellular ATP in intercellular communication and psychiatric diseases.

中文翻译：

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细胞外 ATP 是一种稳态信使，在生理过程和精神疾病中介导细胞间通讯


神经元活动是大脑中信息编码和处理的基础。在神经元激活过程中，产生细胞内 ATP（三磷酸腺苷）以满足高能量需求。同时，ATP 被分泌，增加细胞外 ATP 浓度并充当稳态信使，介导细胞间通讯以防止神经系统异常过度兴奋。除了突触间隙内经典神经递质的局限释放和快速突触信号传导外，ATP 还可以由所有脑细胞释放，广泛扩散，并靶向神经元和神经胶质细胞上不同类型的嘌呤能受体，从而可以协调脑神经元活动并参与各种生理过程，例如睡眠和觉醒， 学习和记忆，以及喂养。细胞外 ATP 的失调导致对神经网络的不稳定作用，正如在许多精神疾病的病因病理学中发现的那样，包括抑郁症、焦虑症、精神分裂症和自闭症谱系障碍。在这篇综述中，我们总结了对细胞外 ATP 作为细胞间信号分子调节神经活动的机制的理解进展，重点是它如何维持神经网络的稳态。特别是，我们还关注由细胞外 ATP 失调引起的神经活动问题，并提出细胞外 ATP 的异常水平可能在某些精神疾病的病因病理学中发挥作用，突出了 ATP 信号在治疗这些精神疾病中的潜在治疗靶点。 最后，我们提出了进一步阐明细胞外 ATP 在细胞间通讯和精神疾病中的作用的潜在途径。