Evidence map›Paper›PMID 37028517›Full record

ArticleBehavioural brain research2023

Histone deacetylase 1 regulates haloperidol-induced motor side effects in aged mice.

Bryan M McClarty, Saikat Chakraborty, Guadalupe Rodriguez, Hongxin Dong

Open access · hybridAbstract read
In one paragraph

Article in Behavioural brain research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
–field-weighted citation impact, top 78% 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

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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

0 citing papers in PubMed, 0 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

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5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Bryan M McClartyDepartments of Psychiatry and Behavioral Sciences, and Neurology, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Ward 7-103, Chicago, IL 60611, USA.
Saikat ChakrabortyDepartments of Psychiatry and Behavioral Sciences, and Neurology, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Ward 7-103, Chicago, IL 60611, USA.
Guadalupe RodriguezDepartments of Psychiatry and Behavioral Sciences, and Neurology, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Ward 7-103, Chicago, IL 60611, USA.
Hongxin DongDepartments of Psychiatry and Behavioral Sciences, and Neurology, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Ward 7-103, Chicago, IL 60611, USA. Electronic address: h-dong@northwestern.edu.
Northwestern University · US

Funding

Molecular Mechanisms Underlying Behavioral and Psychological Symptoms in Alzheimers DiseaseR01AG062249 · NIA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI DONG, HONGXIN, WILSON, ROBERT S · 2018 to 2022
$3.5M
Epigenetic Regulation in Aging and Alzheimer's DiseaseR01AG079989 · NIA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Hongxin Dong · 2023 to 2026
$2.6M
Age-Related Histone Modification Effect on Antipsychotic ActionR01MH109466 · NIMH · NORTHWESTERN UNIVERSITY AT CHICAGO · PI DONG, HONGXIN · 2016 to 2020
$2.1M
Aging and Antipsychotic Efficacy - Epigenetic MechanismsR21MH100919 · NIMH · NORTHWESTERN UNIVERSITY AT CHICAGO · PI DONG, HONGXIN · 2013 to 2014
$425k
NIA NIH HHS R01 AG062249NIA NIH HHS R01 AG079989NIMH NIH HHS R01 MH109466NIMH NIH HHS R21 MH100919
6 · The paper itself

Abstract

backgroundAntipsychotic drugs prescribed to elderly patients with neuropsychiatric disorders often experience severe extrapyramidal side effects. Previous studies from our group suggest that changes in histone modifications during aging increase the risk for antipsychotic drug side effects, because co-administration of antipsychotics with class 1 histone deacetylase (HDAC) inhibitors could mitigate the severity of motor side effects in aged mice. However, which HDAC subtype contributes to the age-related sensitivity to antipsychotic drug side effects is unknown.

methodsIn this study, we overexpressed histone deacetylase type 1(HDAC1) in the striatum of 3-month-old mice and knocked down HDAC 1 in the striatum of 21-month-old mice by microinjection of AAV9-HDAC1-GFP or AAV9-CRISPR/Cas9-HDAC1-GFP vectors. Four weeks after the viral-vector delivery, the typical antipsychotic drug haloperidol was administered daily for 14 days, followed by motor function assessments through the open field, rotarod, and catalepsy behavioral tests.

resultsYoung mice with overexpressed HDAC1 showed increased cataleptic behavior induced by haloperidol administration, which is associated with the increased HDAC1 level in the striatum. In contrast, aged mice with HDAC1 knocked down rescued locomotor activity, motor coordination, and decreased cataleptic behavior induced by haloperidol administration, which is associated with decreased HDAC1 level in the striatum.

conclusionsOur results suggest that HDAC1 is a critical regulator in haloperidol-induced severe motor side effects in aged mice. Repression of HDAC1 expression in the striatum of aged mice could mitigate typical antipsychotic drug-induced motor side effects.

Indexed as

Antipsychotic AgentsDrug-Related Side Effects and Adverse ReactionsHaloperidolHistone Deacetylase 1AnimalsHistone Deacetylase InhibitorsMiceAntipsychotic AgentsHaloperidolHistone Deacetylase 1Histone Deacetylase InhibitorsAntipsychoticsGene editingHistone deacetylase 1 (HDAC1)MiceMotor side effects

Identifiers

PMID37028517
PMCPMC10586515
OpenAlexW4362640171

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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.