Escelsior Andrea, Sterlini Bruno, Belvederi Murri Martino, Valente Pierluigi, Amerio Andrea, di Brozolo Manfredo Radicati, da Silva Beatriz Pereira, Amore Mario
Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa.
IRCCS Ospedale Policlinico San Martino.
Psychiatr Genet. 2020 Apr;30(2):39-48. doi: 10.1097/YPG.0000000000000249.
Transient receptor potential vanilloid 1 (TRPV1) is a polymodal cation channel gated by a large array of chemical and physical stimuli and distributed across different brain regions on neuronal and glial cells. Preclinical studies indicate that TRPV1 might be a target for the treatment of anxiety, depression and addictive disorders. The aim of this narrative review is to focus on studies examining the effects of TRPV1 antagonism on neuroinflammation, neuroprotection and epigenetic regulation. Results suggest that TRPV1 modulation leads to pro- or anti-inflammatory effects depending on the cytokine environment and that the TRPV1 antagonism can switch the microglia towards an anti-inflammatory phenotype. Moreover, TRPV1 inhibitors have neuroprotective properties through the regulation of calcium levels. Finally, TRPV1 antagonism exerts regulatory effects on genes involved in synaptic and cognitive functions through histone deacetylase 2 inhibition. These findings highlight different mechanisms that may underlie the efficacy of TRPV1 antagonists in animal models of severe psychiatric disorders.
瞬时受体电位香草酸亚型1（TRPV1）是一种多模态阳离子通道，可被多种化学和物理刺激激活，分布于神经元和神经胶质细胞的不同脑区。临床前研究表明，TRPV1可能是治疗焦虑、抑郁和成瘾性疾病的靶点。本叙述性综述的目的是聚焦于研究TRPV1拮抗作用对神经炎症、神经保护和表观遗传调控的影响。结果表明，TRPV1的调节作用取决于细胞因子环境，可导致促炎或抗炎效应，且TRPV1拮抗作用可使小胶质细胞转变为抗炎表型。此外，TRPV1抑制剂通过调节钙水平具有神经保护特性。最后，TRPV1拮抗作用通过抑制组蛋白脱乙酰酶2对参与突触和认知功能的基因发挥调节作用。这些发现突出了TRPV1拮抗剂在严重精神疾病动物模型中发挥疗效的不同潜在机制。
