A key role of miR-132-5p in the prefrontal cortex for persistent prophylactic actions of (R)-ketamine in mice
Li Ma,Long Wang,Lijia Chang,Jiajing Shan,Youge Qu,Xingming Wang,Xiayun Wan,Yuko Fujita,Kenji Hashimoto +8 more
TLDR
In this article , RNA-sequencing analysis of prefrontal cortex (PFC) revealed that several miRNAs such as miR-132-5p might contribute to sustained prophylactic effects of (R,S)-ketamine.Abstract:
(R,S)-ketamine is known to elicit persistent prophylactic effects in rodent models of depression. However, the precise molecular mechanisms underlying its action remain elusive. Using RNA-sequencing analysis, we searched for novel molecular target(s) that contribute to the prophylactic effects of (R)-ketamine, a more potent enantiomer of (R,S)-ketamine in chronic restraint stress (CRS) model. Pretreatment with (R)-ketamine (10 mg/kg, 1 day before CRS) significantly ameliorated body weight loss, increased immobility time of forced swimming test, and decreased sucrose preference of sucrose preference test in CRS-exposed mice. RNA-sequencing analysis of prefrontal cortex (PFC) revealed that several miRNAs such as miR-132-5p might contribute to sustained prophylactic effects of (R)-ketamine. Methyl CpG binding protein 2 (MeCP2) is known to regulate brain-derived neurotrophic factor (BDNF) expression. Quantitative RT-PCR confirmed that (R)-ketamine significantly attenuated altered expression of miR-132-5p and its regulated genes (Bdnf, Mecp2, Tgfb1, Tgfbr2) in the PFC of CRS-exposed mice. Furthermore, (R)-ketamine significantly attenuated altered expression of BDNF, MeCP2, TGF-β1 (transforming growth factor β1), and synaptic proteins (PSD-95, and GluA1) in the PFC of CRS-exposed mice. Administration of agomiR-132-5p decreased the expression of Bdnf and Tgfb1 in the PFC, resulting in depression-like behaviors. In contrast, administration of antagomiR-132-5p blocked the increased expression of miR-132-5p and decreased expression of Bdnf in the PFC of CRS-exposed mice, resulting in antidepressant-like effects. In conclusion, our data show a novel role of miR-132-5p in the PFC underlying depression-like phenotypes in CRS model and the sustained prophylactic effects of (R)-ketamine. read more
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Inflammation, stress and depression: an exploration of ketamine's therapeutic profile.
Jenessa Johnston,Maximillian Greenwald,Ioline D. Henter,Christoph Kraus,Anahit Mkrtchian,Neil G Clark,Lawrence Park,Philip W. Gold,Carlos A. Zarate,Bashkim Kadriu +9 more
TL;DR: In this article , the relationship between stress and central nervous system (CNS) inflammation was investigated in the peripheral inflammatory biomarkers of individuals with depression, and it was shown that stress-induced proinflammatory states can contribute to the neurobiology of treatment-resistant depression.
Journal ArticleDOI
Role of neurotrophic and growth factors in the rapid and sustained antidepressant actions of ketamine
Satoshi Deyama,Katsuyuki Kaneda +1 more
TL;DR: 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 as mentioned in this paper .
Journal ArticleDOI
Ketamine, benzoate, and sarcosine for treating depression
TL;DR: Sarcosine, benzoate, ketamine, esketamine, and arketamine have been shown to have anti-inflammatory effects by inhibiting microglial activity as mentioned in this paper .
Journal ArticleDOI
Weapons of stress reduction: (R,S)-ketamine and its metabolites as prophylactics for the prevention of stress-induced psychiatric disorders
TL;DR: In this paper , a review of the prophylactic effects of (R,S)-ketamine, the potential mechanisms underlying its protective actions, and possible future directions for translating pro-phylaxis compounds to the clinic is presented.
Journal ArticleDOI
The antidepressant actions of ketamine and its enantiomers.
TL;DR: In this article , a review summarizes some of the most recent preclinical and clinical research regarding the convergent and divergent prophylactic, immediate, and sustained antidepressant effects of (S)- and (R)-ketamine while addressing potential differences in their side effect and misuse liability profiles.
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