{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kawatake-Kuno A"],"funding":["Shionogi and Co Ltd","AMED","NIMH NIH HHS","NIH","Japan Society for the Promotion of Science"],"pagination":["1265-1285.e10"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11031324"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["112(8)"],"pubmed_abstract":["Despite the rapid and sustained antidepressant effects of ketamine and its metabolites, their underlying cellular and molecular mechanisms are not fully understood. Here, we demonstrate that the sustained antidepressant-like behavioral effects of (2S,6S)-hydroxynorketamine (HNK) in repeatedly stressed animal models involve neurobiological changes in the anterior paraventricular nucleus of the thalamus (aPVT). Mechanistically, (2S,6S)-HNK induces mRNA expression of extrasynaptic GABA<sub>A</sub> receptors and subsequently enhances GABA<sub>A</sub>-receptor-mediated tonic currents, leading to the nuclear export of histone demethylase KDM6 and its replacement by histone methyltransferase EZH2. This process increases H3K27me3 levels, which in turn suppresses the transcription of genes associat"],"journal":["Neuron"],"pubmed_title":["Sustained antidepressant effects of ketamine metabolite involve GABAergic inhibition-mediated molecular dynamics in aPVT glutamatergic neurons."],"pmcid":["PMC11031324"],"funding_grant_id":["JP21K07593","JP21K19707","R01MH118297","JP23ak0101197","JP22H03532","JP21H05173","JP22dm0307102","R01 MH118297","JP21H02849","JP21H00198","JP23K05978","R01 MH119523"],"pubmed_authors":["Ishimori E","Narumiya S","Li H","Inaba H","Uchida S","Hikosaka M","Morishita H","Ohtsuki G","Ueki T","Kawatake-Kuno A","Oishi N","Garkun Y","Murai T"],"additional_accession":[]},"is_claimable":false,"name":"Sustained antidepressant effects of ketamine metabolite involve GABAergic inhibition-mediated molecular dynamics in aPVT glutamatergic neurons.","description":"Despite the rapid and sustained antidepressant effects of ketamine and its metabolites, their underlying cellular and molecular mechanisms are not fully understood. Here, we demonstrate that the sustained antidepressant-like behavioral effects of (2S,6S)-hydroxynorketamine (HNK) in repeatedly stressed animal models involve neurobiological changes in the anterior paraventricular nucleus of the thalamus (aPVT). Mechanistically, (2S,6S)-HNK induces mRNA expression of extrasynaptic GABA<sub>A</sub> receptors and subsequently enhances GABA<sub>A</sub>-receptor-mediated tonic currents, leading to the nuclear export of histone demethylase KDM6 and its replacement by histone methyltransferase EZH2. This process increases H3K27me3 levels, which in turn suppresses the transcription of genes associat","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Apr","modification":"2026-06-01T12:57:45.162Z","creation":"2026-04-08T12:38:02.797Z"},"accession":"S-EPMC11031324","cross_references":{"pubmed":["38377990"],"doi":["10.1016/j.neuron.2024.01.023"]}}