The Effects of Histone Deacetylase Inhibition on the Levels of Cerebral Cytokines in an Animal Model of Mania Induced by Dextroamphetamine.
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-α)) 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.
Laboratory of Neuronal Signaling and Psychopharmacology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC University), Criciúma, SC, Brazil. samiravalvassori@unesc.net.|Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil. samiravalvassori@unesc.net.
Samira S
SS
Valvassori
Laboratory of Neuronal Signaling and Psychopharmacology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC University), Criciúma, SC, Brazil.|Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil.
Wilson R
WR
Resende
Laboratory of Neuronal Signaling and Psychopharmacology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC University), Criciúma, SC, Brazil.|Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil.
Roger B
RB
Varela
Laboratory of Neuronal Signaling and Psychopharmacology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC University), Criciúma, SC, Brazil.
Camila O
CO
Arent
Laboratory of Neuronal Signaling and Psychopharmacology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC University), Criciúma, SC, Brazil.
Fernanda F
FF
Gava
Laboratory of Neuronal Signaling and Psychopharmacology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC University), Criciúma, SC, Brazil.|Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil.
Bruna R
BR
Peterle
Laboratory of Neuronal Signaling and Psychopharmacology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC University), Criciúma, SC, Brazil.
Gustavo C
GC
Dal-Pont
Translational Psychiatry Research Group and Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
André F
AF
Carvalho
Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, Brazil.
Monica L
ML
Andersen
Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil.|Bipolar Disorder Program, Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil.|Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston (UTHealth) Medical School, Houston, TX, USA.|Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston (UTHealth) Medical School, Houston, TX, USA.|Neuroscience Graduate Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA.
João
J
Quevedo
D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D003913:Dextroamphetamine; D004195:Disease Models, Animal; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006655:Histone Deacetylases / Q000378:metabolism*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D018692:Antimanic Agents; D016207:Cytokines; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D003913:Dextroamphetamine
Animal model of mania; Bipolar disorder; Cytokines; Histone deacetylase; Sodium butyrate, valproate