Purinergic system dysfunction in mood disorders: a key target for developing improved therapeutics.
Purinergic system dysfunction in mood disorders: a key target for developing improved therapeutics.
复制标题
情绪障碍的嘌呤能系统功能障碍：开发改进的治疗剂的关键目标。
DOI：
10.1016/j.pnpbp.2014.10.016
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发表时间：
2015-03-03
影响因子：
5.6
通讯作者：
Machado-Vieira, Rodrigo
中科院分区：
文献类型：
--
作者：
Ortiz, Robin;Ulrich, Henning;Zarate, Carlos A., Jr.;Machado-Vieira, Rodrigo
尿酸和嘌呤（如腺苷）调节情绪、睡眠、活动、食欲、认知、记忆、惊厥阈值、社会互动、驱动力和冲动。一个世纪前，人们首次提出嘌呤能功能障碍和情绪障碍之间的联系。有趣的是，最近的一项全国性人群研究显示，双相情感障碍（BD）受试者的痛风风险升高，最近对辅助嘌呤能调节剂的安慰剂对照试验的荟萃分析和系统评价证实了它们在双相躁狂中的益处。尿酸可以调节能量和活动水平，较高的水平与较高的能量和BD谱相关。最近的几项遗传学研究表明，嘌呤能系统，特别是P1和P2受体亚型的调节，在情绪障碍中起着重要作用，这一模型得到了证实。核苷酸浓度可以使用脑光谱学测量，并且已经开发了用于腺苷（P1）受体的体内正电子发射断层扫描（PET）成像的配体，从而允许潜在的靶点接合研究。本文综述了嘌呤能系统在心境障碍的病理生理中的重要作用。关注这个有前途的治疗靶点可能会导致开发具有抗抑郁、情绪稳定和认知作用的治疗方法。
Uric acid and purines (such as adenosine) regulate mood, sleep, activity, appetite, cognition, memory, convulsive threshold, social interaction, drive, and impulsivity. A link between purinergic dysfunction and mood disorders was first proposed a century ago. Interestingly, a recent nationwide population-based study showed elevated risk of gout in subjects with bipolar disorder (BD), and a recent meta-analysis and systematic review of placebo-controlled trials of adjuvant purinergic modulators confirmed their benefits in bipolar mania. Uric acid may modulate energy and activity levels, with higher levels associated with higher energy and BD spectrum. Several recent genetic studies suggest that the purinergic system particularly the modulation of P1 and P2 receptor subtypes—plays a role in mood disorders, lending credence to this model. Nucleotide concentrations can be measured using brain spectroscopy, and ligands for in vivo positron emission tomography (PET) imaging of adenosine (P1) receptors have been developed, thus allowing potential target engagement studies. This review discusses the key role of the purinergic system in the pathophysiology of mood disorders. Focusing on this promising therapeutic target may lead to the development of therapies with antidepressant, mood stabilization, and cognitive effects.
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影响因子：
7.3
作者：
Bhattacharya, Anindya;Wang, Qi;Letavic, Michael A.
通讯作者：
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影响因子：
9.3
作者：
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作者：
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DOI：
10.3233/jad-2010-1330
发表时间：
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期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
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通讯作者：
Quinn JF
影响因子：
5.4
作者：
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通讯作者：
Osby, Urban