Evidence map›Paper›PMID 30102916›Full record

ArticleExperimental neurology2018

Targeting histone deacetylation for recovery of maternal deprivation-induced changes in BDNF and AKAP150 expression in the VTA.

Ryan D Shepard, Shawn Gouty, Haifa Kassis, Aylar Berenji, William Zhu, Brian M Cox, Fereshteh S Nugent

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Experimental neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.5field-weighted citation impact, top 10% 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

27 citing papers in PubMed, 38 citations in OpenAlex.

  1. Article
  2. Article
  3. Epigenetic regulation of brain development, plasticity, and response to early-life stress.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Biosensors, Recent Advances in Determination of BDNF and NfL.Cellular and molecular neurobiology · 2023
    Review
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  10. Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Review
  18. Article
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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

7 authors at 1 institution in 1 country.

Ryan D ShepardUniformed Services University of the Health Sciences, Department of Pharmacology, Bethesda, MD 20814, USA.
Shawn GoutyUniformed Services University of the Health Sciences, Department of Pharmacology, Bethesda, MD 20814, USA.
Haifa KassisUniformed Services University of the Health Sciences, Department of Pharmacology, Bethesda, MD 20814, USA.
Aylar BerenjiUniformed Services University of the Health Sciences, Department of Pharmacology, Bethesda, MD 20814, USA.
William ZhuUniformed Services University of the Health Sciences, Department of Pharmacology, Bethesda, MD 20814, USA.
Brian M CoxUniformed Services University of the Health Sciences, Department of Pharmacology, Bethesda, MD 20814, USA.
Fereshteh S NugentUniformed Services University of the Health Sciences, Department of Pharmacology, Bethesda, MD 20814, USA. Electronic address: fereshteh.nugent@usuhs.edu.
Uniformed Services University of the Health Sciences · US

Funding

Effects of early life stress on synaptic function and DA signaling in the VTAR01DA039533 · NIDA · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · PI NUGENT, FERESHTEH S · 2015 to 2019
$1.8M
NIDA NIH HHS R01 DA039533
6 · The paper itself

Abstract

Severe early life stressors increase the probability of developing psychiatric disorders later in life through modifications in neuronal circuits controlling brain monoaminergic signaling. Our previous work demonstrated that 24 h maternal deprivation (MD) in male Sprague Dawley rats modifies dopamine (DA) signaling from the ventral tegmental area (VTA) through changes at GABAergic synapses that were reversible by in vitro histone deacetylase (HDAC) inhibition which led to restoration of the scaffold A-kinase anchoring protein (AKAP150) signaling and subsequently recovered GABAergic plasticity (Authement et al., 2015). Using a combination of in situ hybridization, Western blots and immunohistochemistry, we confirmed that MD-induced epigenetic modifications at the level of histone acetylation were associated with an upregulation of HDAC2. MD also increased Akap5 mRNA levels in the VTA. Western blot analysis of AKAP150 protein expression showed an increase in synaptic levels of AKAP150 protein in the VTA with an accompanying decrease in synaptic levels of protein kinase A (PKA). Moreover, the abundance of mature brain-derived neurotrophic factor (BDNF) protein of VTA tissues from MD rats was significantly lower than in control groups. In vivo systemic injection with a selective class I HDAC inhibitor (CI-994) was sufficient to reverse MD-induced histone hypoacetylation in the VTA for 24 h after the injection. Furthermore, HDAC inhibition normalized the levels of mBDNF and AKAP150 proteins at 24 h. Our data suggest that HDAC-mediated targeting of BDNF and AKAP-dependent local signaling within VTA could provide novel therapeutics for prevention of later-life psychopathology.

Indexed as

Maternal DeprivationAcetylationA Kinase Anchor ProteinsAnimalsBrain-Derived Neurotrophic FactorDopamineEnzyme InhibitorsGene Expression RegulationHistone Deacetylase 2HistonesIn Vitro TechniquesMaleRatsRats, Sprague-DawleyRNA, MessengerSubcellular FractionsAkap5 protein, ratA Kinase Anchor ProteinsBrain-Derived Neurotrophic FactorDopamineEnzyme InhibitorsHdac2 protein, ratHistone Deacetylase 2HistonesRNA, MessengerTyrosine 3-MonooxygenaseA-kinase anchoring protein (AKAP)Brain derived neurotrophic factor (BDNF)DopamineEarly life stressEpigeneticsHistone acetylationHistone deacetylase (HDAC)Histone deacetylase inhibitor (HDAC inhibitor)Maternal deprivation (MD)Ventral tegmental area (VTA)

Identifiers

PMID30102916
PMCPMC6139260
OpenAlexW2887479338

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.