Department of Pharmacobiology, Jagiellonian University Medical College, Medyczna 9, PL 30-688 Krakow, Poland.
Curr Neuropharmacol. 2021;19(11):2012-2019. doi: 10.2174/1570159X19666210225153404.
As one of the most important elements in our body, zinc plays a part in both the pathophysiology of depression and the antidepressant response. Patients suffering from major depression show significantly reduced zinc levels, which are normalized following successful antidepressant treatment. Recent studies have shown the interaction between zinc, GPR39 and neuropeptides, including galanin and neuropeptide Y (NPY). The zinc-sensing receptor GPR39 forms heterotrimers with 5-HT and the galanin receptor GalR upon their co-expression in mammalian cells. The oligomerization of these heterotrimers is regulated by the zinc concentration, and this may have an influence on depressive-like behavior. The antidepressant-like effect of zinc is linked to elevated levels of brain-derived neurotrophic factor (BDNF) in brain structures associated with emotion, such as the hippocampus and the amygdala. BDNF regulates neuropeptides, including NPY, cholecystokinin (CCK), and substance P or galanin, which are also implicated in mood disorders. This review focuses for the first time on the interaction between zinc, the GPR39 zinc receptor, BDNF and selected neuropeptides in terms of depression in order to determine its possible role in the neuropharmacology of that illness.
锌作为我们体内最重要的元素之一，在抑郁症的病理生理学和抗抑郁反应中都起着作用。患有重度抑郁症的患者表现出明显降低的锌水平，而成功的抗抑郁治疗后锌水平会恢复正常。最近的研究表明，锌、GPR39 和神经肽之间存在相互作用，包括甘丙肽和神经肽 Y（NPY）。锌感应受体 GPR39 在哺乳动物细胞中与 5-HT 和甘丙肽受体 GalR 共同表达时，形成异三聚体。这些异三聚体的寡聚化受锌浓度调节，这可能对抑郁样行为有影响。锌的抗抑郁作用与脑源性神经营养因子（BDNF）在与情绪相关的脑结构（如海马体和杏仁核）中的水平升高有关。BDNF 调节神经肽，包括 NPY、胆囊收缩素（CCK）和 P 物质或甘丙肽，它们也与情绪障碍有关。本综述首次重点关注锌、GPR39 锌受体、BDNF 和选定神经肽之间的相互作用，以确定其在该疾病神经药理学中的可能作用。
