Nucleocytoplasmic export of HDAC5 and SIRT2 downregulation: two epigenetic mechanisms by which antidepressants enhance synaptic plasticity markers.
Rationale: Antidepressant action has been linked to increased synaptic plasticity in which epigenetic mechanisms such as histone posttranslational acetylation could be involved. Interestingly, the histone deacetylases HDAC5 and SIRT2 are oppositely regulated by stress and antidepressants in mice pre...
| Publicado en: | Psychopharmacology Vol. 235; no. 10; pp. 2831 - 2847 |
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| Autores principales: | , , , , , , , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
Oct2018
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=132021641&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 132021641 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00333158 EJD jtl: Psychopharmacology issn: 00333158 maglogo: N pubinfo: dt: Oct2018 vid: 235 iid: 10 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 132021641 10.1007/s00213-018-4975-8 132021641 ppf: 2831 ppct: 16 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Nucleocytoplasmic export of HDAC5 and SIRT2 downregulation: two epigenetic mechanisms by which antidepressants enhance synaptic plasticity markers. aug: au: Muñoz-Cobo, I. Erburu, M.M. Zwergel, C. Cirilli, R. Mai, A. Valente, S. Puerta, E. Tordera, Rosa M. affil: Department of Pharmacology and Toxicology, University of Navarra, C/ Irunlarrea 1, 31010, Pamplona, Spain sug: ab: Rationale: Antidepressant action has been linked to increased synaptic plasticity in which epigenetic mechanisms such as histone posttranslational acetylation could be involved. Interestingly, the histone deacetylases HDAC5 and SIRT2 are oppositely regulated by stress and antidepressants in mice prefrontal cortex (PFC). Besides, the neuroblastoma SH-SY5Y line is an in vitro neuronal model reliable to study drug effects with clear advantages over animals.Objectives: We aimed to characterize in vitro the role of HDAC5 and SIRT2 in antidepressant regulation of neuroplasticity.Methods: SH-SY5Y cultures were incubated with imipramine, fluoxetine, and reboxetine (10 μM, 2 and 24 h) as well as the selective HDAC5 (MC3822, 5 μM, 24 h) or SIRT2 (33i, 5 μM, 24 h) inhibitors. The regulation of the brain-derived neurotrophic factor (BDNF), the vesicular glutamate transporter 1 (VGLUT1), the acetylated histones 3 (AcH3) and 4 (AcH4), HDAC5, and SIRT2 was studied. Comparatively, the long-term effects of these antidepressants (21 days, i.p.) in the mice (C57BL6, 8 weeks) PFC were studied.Results: Antidepressants increased both in vitro and in vivo expression of BDNF, VGLUT1, AcH3, and AcH4. Moreover, imipramine and reboxetine increased the phosphorylated form of HDAC5 (P-HDAC5), mediating its cytoplasmic export. Further, SIRT2 was downregulated by all antidepressants. Finally, specific inhibition of HDAC5 and SIRT2 increased neuroplasticity markers.Conclusions: This study supports the validity of the SH-SY5Y model for studying epigenetic changes linked to synaptic plasticity induced by antidepressants as well as the effect of selective HDAC inhibitors. Particularly, nucleocytoplasmic export of HDAC5 and SIRT2 downregulation mediated by antidepressants could enhance synaptic plasticity markers leading to antidepressant action. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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