Modulation of the aquaporin 4 (AQP4) water-regulatory channel or production of autoantibodies against this protein have been implicated in a variety of neuropsychiatric conditions, and possible mechanisms have been proposed. However, the nature of the interaction between AQP4 expression and its implications in depression remain elusive. To our knowledge, this is the first review summarising data for the involvement of AQP4 in the context of depression and related mechanisms across a wide range of experimental studies: pre-clinical (KO and wild-type), post-mortem, ex vivo, and clinical studies in depression. Overall, preclinical AQP4 wild-type studies showed that exposure to stress or inflammation, used as models of depression, decreased AQP4 protein and gene expression in various brain regions, including prefrontal cortex (PFC), choroid plexus and, especially, hippocampus. In preclinical AQP4 KO studies, AQP4 expression is necessary to prevent the effect of stress and inflammation on reduced neurogenesis and gliogenesis, and increased apoptosis and depressive-like behaviours. While in post-mortem and ex vivo studies of depression AQP4 expression was usually decreased in the hippocampus, prefrontal cortex and locus coeruleus, in clinical studies, where mRNA AQP4 expression or serum AQP4 autoantibodies were measured, there were no differences in depressed patients when compared with controls. In the future, studies should further investigate the mechanisms underlying the action of AQP4, and continue exploring if AQP4 autoantibodies are either contributing or underlying mechanisms of depression, or whether they are simply a mechanism underlying other autoimmune conditions where depression is present.

水通道蛋白 4 (AQP4) 水调节通道的调节或针对该蛋白的自身抗体的产生与多种神经精神疾病有关，并且已经提出了可能的机制。然而，AQP4 表达之间相互作用的性质及其对抑郁症的影响仍然难以捉摸。据我们所知，这是第一个总结 AQP4 参与抑郁症和相关机制的数据的综述，涉及广泛的实验研究：临床前（KO 和野生型）、死后、离体、和临床研究抑郁症。总体而言，临床前 AQP4 野生型研究表明，暴露于压力或炎症（用作抑郁症模型）会降低不同大脑区域的 AQP4 蛋白和基因表达，包括前额叶皮层 (PFC)、脉络丛，尤其是海马体。在临床前 AQP4 KO 研究中，AQP4 的表达对于防止压力和炎症对神经发生和胶质细胞生成减少以及细胞凋亡和抑郁样行为增加的影响是必要的。在尸检和体外抑郁症的研究 AQP4 表达通常在海马、前额叶皮层和蓝斑中减少，在临床研究中，测量 mRNA AQP4 表达或血清 AQP4 自身抗体时，与对照组相比，抑郁症患者没有差异。未来，研究应进一步研究 AQP4 作用的潜在机制，并继续探索 AQP4 自身抗体是否是抑郁症的促成机制或潜在机制，或者它们是否仅仅是其他存在抑郁症的自身免疫性疾病的潜在机制。