The Effects of Histone Deacetylase Inhibition on the Levels of Cerebral Cytokines in an Animal Model of Mania Induced by Dextroamphetamine

The Effects of Histone Deacetylase Inhibition on the Levels of Cerebral Cytokines in an Animal Model of Mania Induced by Dextroamphetamine

Author Valvassori, Samira S. Google Scholar
Resende, Wilson R. Google Scholar
Varela, Roger B. Google Scholar
Arent, Camila O. Google Scholar
Gava, Fernanda F. Google Scholar
Peterle, Bruna R. Google Scholar
Dal-Pont, Gustavo C. Google Scholar
Carvalho, Andre F. Google Scholar
Andersen, Monica L. Autor UNIFESP Google Scholar
Quevedo, Joao Google Scholar
Abstract Studies have suggested the involvement of inflammatory processes in the physiopathology of bipolar disorder. Preclinical evidences have shown that histone deacetylase inhibitors may act as mood-stabilizing agents and protect the brain in models of mania and depression. The aim of the present study was to evaluate the effects of sodium butyrate (SB) and valproate (VPA) on behavioral changes, histone deacetylase activity, and the levels of cytokines in an animal model of mania induced by dextroamphetamine (d-AMPH). Wistar rats were first given d-AMPH or saline (Sal) for a period of 14 days, and then, between the 8th and 14th days, the rats were treated with SB, VPA, or Sal. The activity of histone deacetylase and the levels of cytokines (interleukin (IL) IL-4, IL-6, and IL-10 and tumor necrosis factor-alpha (TNF-alpha)) were evaluated in the frontal cortex and striatum of the rats. The administration of d-AMPH increased the activity of histone deacetylase in the frontal cortex. Administration of SB or VPA decreased the levels of histone deacetylase activity in the frontal cortex and striatum of rats. SB per se increased the levels of cytokines in both of the brain structures evaluated. AMPH increased the levels of cytokines in both of the brain structures evaluated, and VPA reversed this alteration. The effects of SB on d-AMPH-induced cytokine alterations were dependent on the brain structure and the cytokine evaluated. Despite VPA and SB having a similar mechanism of action, both being histone deacetylase inhibitors, they showed different effects on the levels of cytokines. The present study reinforces the need for more research into histone deacetylase inhibitors being used as a possible target for new medications in the treatment of bipolar disorder.
Keywords Bipolar disorder
Cytokines
Animal model of mania
Histone deacetylase
Sodium butyrate,valproate
xmlui.dri2xhtml.METS-1.0.item-coverage Totowa
Language English
Date 2018
Published in Molecular Neurobiology. Totowa, v. 55, n. 2, p. 1430-1439, 2018.
ISSN 0893-7648 (Sherpa/Romeo, impact factor)
Publisher Humana Press Inc
Extent 1430-1439
Origin http://dx.doi.org/10.1007/s12035-017-0384-y
Access rights Closed access
Type Article
Web of Science ID WOS:000425624000044
URI https://repositorio.unifesp.br/handle/11600/54187

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