Journal Article

The neurobiological mechanisms and therapeutic prospect of extracellular ATP in depression

Zhao, Wenjing, Huang, Li, Yang, Xinxin, Ding, Yuanyuan, Ma, Lulin, Zhang, Tianhao, Wang, Kaixin, Chen, Xiangdong, Huang, Shiqian, Fu, Daan, Deng, Daling, Zhang, Yanyan

2024

Overview

Background Depression is a prevalent psychiatric disorder with high long‐term morbidities, recurrences, and mortalities. Despite extensive research efforts spanning decades, the cellular and molecular mechanisms of depression remain largely unknown. What's more, about one third of patients do not have effective anti‐depressant therapies, so there is an urgent need to uncover more mechanisms to guide the development of novel therapeutic strategies. Adenosine triphosphate (ATP) plays an important role in maintaining ion gradients essential for neuronal activities, as well as in the transport and release of neurotransmitters. Additionally, ATP could also participate in signaling pathways following the activation of postsynaptic receptors. By searching the website PubMed for articles about “ATP and depression” especially focusing on the role of extracellular ATP (eATP) in depression in the last 5 years, we found that numerous studies have implied that the insufficient ATP release from astrocytes could lead to depression and exogenous supply of eATP or endogenously stimulating the release of ATP from astrocytes could alleviate depression, highlighting the potential therapeutic role of eATP in alleviating depression. Aim Currently, there are few reviews discussing the relationship between eATP and depression. Therefore, the aim of our review is to conclude the role of eATP in depression, especially focusing on the evidence and mechanisms of eATP in alleviating depression. Conclusion We will provide insights into the prospects of leveraging eATP as a novel avenue for the treatment of depression. The knock out of adenosine triphosphate (ATP) release channel (Panx1, Calhm2) and IP3R2, which could lead to the decreased extracellular ATP concentration, will exert depressive‐like effects. This means extracellular ATP may play an important role in depression. Purinergic receptors play vital roles in depression. The activation of P2X2R and P2X4R may play important roles in anti‐depressant effects, while P2X7R signaling could potentially promote the development of depressive‐like behaviors. Both A1 receptors and A2a receptors have been found to play a significant role in depression. A2a receptor antagonists have been reported to have clear anti‐depressant effects.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: Adenosine / Adenosine triphosphate / Adenosine Triphosphate - metabolism / anti‐depressant therapy / Apolipoproteins / Astrocytes / Astrocytes - metabolism / Behavior / Comorbidity / depression / Depression - drug therapy / Disease / Drug dosages / eATP / Humans / MDD / Mental depression / Metabolism / mitochondria / Molecular modelling / Neurogenesis / P2X7R / purinergic receptors / Review / Reviews