Role of neurotrophic and growth factors in the rapid and sustained antidepressant actions of ketamine. (15th February 2023)

• Record Type: Journal Article
• Authors: Deyama, Satoshi; Kaneda, Katsuyuki
• Is Part Of: Neuropharmacology. Volume 224(2023)
• Publication Date: 2023-02-15
• Subjects: BDNF -- Depression -- IGF-1 -- Ketamine -- Rapid antidepressants -- VEGF-A; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2022.109335
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: 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'. Highlights: Decreased levels of BDNF and VEGF are linked with the pathophysiology of depression. Ketamine-induced rapid BDNF/VEGF release in the mPFC mediates its antidepressant-like actions. Hippocampal BDNF/VEGF signaling plays a role in the antidepressant-like actions of ketamine. Ketamine-induced persistent IGF-1 release in the mPFC mediates its antidepressant-like actions.