Evidence map›Paper›PMID 30091005›Full record

ArticlePsychopharmacology2018

Nucleocytoplasmic export of HDAC5 and SIRT2 downregulation: two epigenetic mechanisms by which antidepressants enhance synaptic plasticity markers.

I Muñoz-Cobo, M M Erburu, C Zwergel, R Cirilli, A Mai, S Valente, E Puerta, Rosa M Tordera

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Article in Psychopharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.7field-weighted citation impact, top 29% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 15 citations in OpenAlex.

  1. Review
  2. Inhibiting silence information regulator 2 and glutaminase in the amygdala can improve social behavior in autistic rats.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

I Muñoz-CoboDepartment of Pharmacology and Toxicology, University of Navarra, C/ Irunlarrea 1, 31010, Pamplona, Spain.
M M ErburuDepartment of Pharmacology and Toxicology, University of Navarra, C/ Irunlarrea 1, 31010, Pamplona, Spain.
C ZwergelDepartment of Drug Chemistry and Technologies, Sapienza University of Rome, Rome, Italy.
R CirilliIstituto Superiore di Sanità, Sapienza University of Rome, Rome, Italy.
A MaiDepartment of Drug Chemistry and Technologies, Sapienza University of Rome, Rome, Italy.
S ValenteDepartment of Drug Chemistry and Technologies, Sapienza University of Rome, Rome, Italy.
E PuertaDepartment of Pharmacology and Toxicology, University of Navarra, C/ Irunlarrea 1, 31010, Pamplona, Spain.
Rosa M TorderaDepartment of Pharmacology and Toxicology, University of Navarra, C/ Irunlarrea 1, 31010, Pamplona, Spain. rtordera@unav.es.ORCID http://orcid.org/0000-0002-3564-4135
Universidad de Navarra · ESSapienza University of Rome · ITIstituto Superiore di Sanità · IT

Funding

Secretaría de Estado de Investigación, Desarrollo e Innovación BES-2012-052190Secretaría de Estado de Investigación, Desarrollo e Innovación SAF2011-27910
6 · The paper itself

Abstract

rationaleAntidepressant 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.

objectivesWe aimed to characterize in vitro the role of HDAC5 and SIRT2 in antidepressant regulation of neuroplasticity.

methodsSH-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.

resultsAntidepressants 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.

conclusionsThis 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.

Indexed as

AnimalsAntidepressive AgentsDown-RegulationEpigenesis, GeneticFluoxetineHistone Deacetylase InhibitorsHistone DeacetylasesHumansImipramineMaleMiceMice, Inbred C57BLNeuronal PlasticityPrefrontal CortexRandom AllocationReboxetineAntidepressive AgentsFluoxetineHdac5 protein, mouseHistone Deacetylase InhibitorsHistone DeacetylasesImipramineReboxetineSirt2 protein, mouseSirtuin 2AntidepressantsHistone deacetylase 5 (HDAC5)Major depressionPrefrontal cortex (PFC)SH-SY5YSirtuin 2 (Sirt2)

Identifiers

PMID30091005
OpenAlexW2887974427

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.