HDAC inhibitors reverse mania-like behavior and modulate epigenetic regulatory enzymes in an animal model of mania induced by Ouabain.
Animals
Behavior, Animal
/ drug effects
Bipolar Disorder
/ drug therapy
Butyric Acid
/ administration & dosage
Corpus Striatum
/ metabolism
DNA (Cytosine-5-)-Methyltransferases
/ metabolism
Disease Models, Animal
Frontal Lobe
/ metabolism
Hippocampus
/ metabolism
Histone Acetyltransferases
/ metabolism
Histone Deacetylase Inhibitors
/ administration & dosage
Histone Deacetylases
/ metabolism
Locomotion
/ drug effects
Male
Mania
/ chemically induced
Ouabain
/ adverse effects
Rats
Rats, Wistar
Signal Transduction
/ drug effects
Treatment Outcome
Valproic Acid
/ administration & dosage
Bipolar disorder
Epigenetics
Mania
Ouabain
Sodium butyrate
Valproate
Journal
Pharmacology, biochemistry, and behavior
ISSN: 1873-5177
Titre abrégé: Pharmacol Biochem Behav
Pays: United States
ID NLM: 0367050
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
29
11
2019
revised:
23
03
2020
accepted:
24
03
2020
pubmed:
31
3
2020
medline:
22
1
2021
entrez:
31
3
2020
Statut:
ppublish
Résumé
The etiology of bipolar disorder (BD) is multifactorial, involving both environmental and genetic factors. Current pharmacological treatment is associated with several side effects, which are the main reason patients discontinue treatment. Epigenetic alterations have been studied for their role in the pathophysiology of BD, as they bridge the gap between gene and environment. Evaluate the effects of histone deacetylase inhibitors on behavior and epigenetic enzymes activity in a rat model of mania induced by ouabain. Adult male rats were subjected to a single intracerebroventricular injection of ouabain (10 Ouabain induced hyperactivity in rats, which was reversed by valproate and sodium butyrate treatment. Ouabain did not alter the activity of any of the enzymes evaluated. However, valproate and sodium butyrate decreased the activity of histone deacetylase and DNA methyltransferase. Moreover, there was a positive correlation between these two enzymes. These results suggest that targeting epigenetic mechanisms may play an important role in mania-like behavior management.
Sections du résumé
BACKGROUND
The etiology of bipolar disorder (BD) is multifactorial, involving both environmental and genetic factors. Current pharmacological treatment is associated with several side effects, which are the main reason patients discontinue treatment. Epigenetic alterations have been studied for their role in the pathophysiology of BD, as they bridge the gap between gene and environment.
OBJECTIVE
Evaluate the effects of histone deacetylase inhibitors on behavior and epigenetic enzymes activity in a rat model of mania induced by ouabain.
METHODS
Adult male rats were subjected to a single intracerebroventricular injection of ouabain (10
RESULTS
Ouabain induced hyperactivity in rats, which was reversed by valproate and sodium butyrate treatment. Ouabain did not alter the activity of any of the enzymes evaluated. However, valproate and sodium butyrate decreased the activity of histone deacetylase and DNA methyltransferase. Moreover, there was a positive correlation between these two enzymes.
CONCLUSION
These results suggest that targeting epigenetic mechanisms may play an important role in mania-like behavior management.
Identifiants
pubmed: 32222371
pii: S0091-3057(19)30587-8
doi: 10.1016/j.pbb.2020.172917
pii:
doi:
Substances chimiques
Histone Deacetylase Inhibitors
0
Butyric Acid
107-92-6
Ouabain
5ACL011P69
Valproic Acid
614OI1Z5WI
DNA (Cytosine-5-)-Methyltransferases
EC 2.1.1.37
Histone Acetyltransferases
EC 2.3.1.48
Histone Deacetylases
EC 3.5.1.98
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
172917Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest JQ has the following declarations of interest: Clinical Research Support: Janssen Pharmaceutical (Clinical Trial), Allergan (Clinical Trial); Advisory Boards, Speaker Bureaus, Expert Witness, or Consultant: Daiichi Sankyo (Speaker Bureau); Patent, Equity, or Royalty: Instituto de Neurociencias Dr. Joao Quevedo (Stockholder); Other: Artmed Editora (Copyright), Artmed Panamericana (Copyright). All the other authors have no conflict of interest.