Garayo-Larrea A, Azqueta A, Tordera R M
Dept. of Pharmaceutical Sciences, Pharmacology Division, Universidad de Navarra, Pamplona, Spain.
Dept. of Pharmaceutical Sciences, Toxicology Division, Universidad de Navarra, Pamplona, Spain.
Neurosci Appl. 2024 Jun 29;3:104081. doi: 10.1016/j.nsa.2024.104081. eCollection 2024.
This paper critically reviews the interesting and extensive knowledge regarding the role of some HDACs in major depression. MD is associated with neuroplasticity failure and inflammatory events, in which, several histone deacetylase (HDACs) enzymes play a key role. Specifically, increased expression of specific HDACs are linked to depressive-like behaviour, repress the expression of the brain derived neurotrophic factor (BDNF), and induce a pro-inflammatory response. Conversely, other HDACs exert an antidepressant action, promote dendritic growth and protect neurons or immune cells from inflammatory events. The right balance between both types is needed to respond correctly to the different physiological/pathological stimuli. However, aberrant expressions or activities of specific HDACs could be associated with MD. Further studies should identify the mechanism by which MD regulates specific HDAC subtypes both in post-mortem brain tissue and in peripheral immune cells.
本文批判性地回顾了有关某些组蛋白去乙酰化酶(HDACs)在重度抑郁症中作用的有趣且广泛的知识。重度抑郁症与神经可塑性衰竭和炎症事件相关,其中几种组蛋白去乙酰化酶(HDACs)发挥关键作用。具体而言,特定HDACs的表达增加与抑郁样行为有关,抑制脑源性神经营养因子(BDNF)的表达,并诱导促炎反应。相反,其他HDACs发挥抗抑郁作用,促进树突生长并保护神经元或免疫细胞免受炎症事件影响。两种类型之间需要正确平衡以对不同的生理/病理刺激做出正确反应。然而,特定HDACs的异常表达或活性可能与重度抑郁症有关。进一步的研究应确定重度抑郁症在死后脑组织和外周免疫细胞中调节特定HDAC亚型的确切机制。