Bartoli Francesco, Burnstock Geoffrey, Crocamo Cristina, Carrà Giuseppe
Department of Medicine and Surgery, University of Milano Bicocca, Via Cadore 48, 20900 Monza, Italy.
Department of Mental Health & Addiction, ASST Nord Milano, Bassini Hospital, via Gorki 50, 20092 Cinisello Balsamo, Milano, Italy.
Brain Sci. 2020 Mar 12;10(3):160. doi: 10.3390/brainsci10030160.
It is established that purinergic signaling can shape a wide range of physiological functions, including neurotransmission and neuromodulation. The purinergic system may play a role in the pathophysiology of mood disorders, influencing neurotransmitter systems and hormonal pathways of the hypothalamic-pituitary-adrenal axis. Treatment with mood stabilizers and antidepressants can lead to changes in purinergic signaling. In this overview, we describe the biological background on the possible link between the purinergic system and depression, possibly involving changes in adenosine- and ATP-mediated signaling at P1 and P2 receptors, respectively. Furthermore, evidence on the possible antidepressive effects of non-selective adenosine antagonist caffeine and other purinergic modulators is reviewed. In particular, A2A and P2X7 receptors have been identified as potential targets for depression treatment. Preclinical studies highlight that both selective A2A and P2X7 antagonists may have antidepressant effects and potentiate responses to antidepressant treatments. Consistently, recent studies feature the possible role of the purinergic system peripheral metabolites as possible biomarkers of depression. In particular, variations of serum uric acid, as the end product of purinergic metabolism, have been found in depression. Although several open questions remain, the purinergic system represents a promising research area for insights into the molecular basis of depression.
已证实嘌呤能信号传导可塑造多种生理功能，包括神经传递和神经调节。嘌呤能系统可能在情绪障碍的病理生理学中发挥作用，影响神经递质系统和下丘脑 - 垂体 - 肾上腺轴的激素途径。使用心境稳定剂和抗抑郁药进行治疗可导致嘌呤能信号传导发生变化。在本综述中，我们描述了嘌呤能系统与抑郁症之间可能联系的生物学背景，这可能分别涉及腺苷和ATP介导的信号在P1和P2受体处的变化。此外，还综述了关于非选择性腺苷拮抗剂咖啡因和其他嘌呤能调节剂可能具有抗抑郁作用的证据。特别是，A2A和P2X7受体已被确定为抑郁症治疗的潜在靶点。临床前研究强调，选择性A2A和P2X7拮抗剂可能都具有抗抑郁作用，并增强对抗抑郁治疗的反应。一致地，最近的研究表明嘌呤能系统外周代谢产物可能作为抑郁症的生物标志物发挥作用。特别是，已发现抑郁症患者中作为嘌呤能代谢终产物的血清尿酸存在变化。尽管仍有几个未解决的问题，但嘌呤能系统是深入了解抑郁症分子基础的一个有前景的研究领域。
