Laboratory of Molecular Pharmacology, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, 920-1192, Japan.
Laboratory of Molecular Pharmacology, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, 920-1192, Japan.
Neuropharmacology. 2023 Feb 15;224:109335. doi: 10.1016/j.neuropharm.2022.109335. Epub 2022 Nov 17.
The neurotrophic hypothesis of depression proposes that reduced levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) contribute to neuronal atrophy or loss in the prefrontal cortex (PFC) and hippocampus and impaired hippocampal adult neurogenesis, which are associated with depressive symptoms. Chronic, but acute, treatment with typical monoaminergic antidepressants can at least partially reverse these deficits, in part via induction of BDNF and/or VEGF expression, consistent with their delayed onset of action. Ketamine, an N-methyl-d-aspartate receptor antagonist, exerts rapid and sustained antidepressant effects. Rodent studies have revealed that ketamine rapidly increases BDNF and VEGF release and/or expression in the PFC and hippocampus, which in turn increases the number and function of spine synapses in the PFC and hippocampal neurogenesis. Ketamine also induces the persistent release of insulin-like growth factor 1 (IGF-1) in the PFC of male mice. These neurotrophic effects of ketamine are associated with its rapid and sustained antidepressant effects. In this review, we first provide an overview of the neurotrophic hypothesis of depression and then discuss the role of BDNF, VEGF, IGF-1, and other growth factors (IGF-2 and transforming growth factor-β1) in the antidepressant effects of ketamine and its enantiomers. This article is part of the Special Issue on 'Ketamine and its Metabolites'.
抑郁的神经营养假说提出，脑源性神经营养因子 (BDNF) 和血管内皮生长因子 (VEGF) 水平降低导致前额叶皮层 (PFC) 和海马体中的神经元萎缩或丧失，以及海马体中的成年神经发生受损，这些都与抑郁症状有关。慢性但急性的典型单胺能抗抑郁药治疗至少可以部分逆转这些缺陷，部分原因是诱导 BDNF 和/或 VEGF 表达，这与它们的延迟作用时间一致。氯胺酮，一种 N-甲基-D-天冬氨酸受体拮抗剂，具有快速和持续的抗抑郁作用。啮齿动物研究表明，氯胺酮可迅速增加 PFC 和海马体中的 BDNF 和 VEGF 释放和/或表达，进而增加 PFC 和海马体中的棘突突触数量和功能。氯胺酮还诱导雄性小鼠 PFC 中胰岛素样生长因子 1 (IGF-1) 的持续释放。氯胺酮的这些神经营养作用与其快速和持续的抗抑郁作用有关。在这篇综述中，我们首先概述了抑郁的神经营养假说，然后讨论了 BDNF、VEGF、IGF-1 和其他生长因子 (IGF-2 和转化生长因子-β1) 在氯胺酮及其对映异构体的抗抑郁作用中的作用。本文是“氯胺酮及其代谢物”特刊的一部分。
