Effects of sodium butyrate in animal models of mania and depression

Abstract

Bipolar disorder is a severe mood disorder with high morbidity and mortality. Despite adequate treatment, patients continue to have recurrent mood episodes, residual symptoms, and functional impairment. Some preclinical studies have shown that histone deacetylase inhibitors may act on depressive-like and manic-like behaviors. Therefore, the aim of the present study was to evaluate the effects of sodium butyrate (SB) on behavioral changes in animal models of depression and mania. The animals were submitted to protocols of chronic mild stress or maternal deprivation for induction of depressive-like behaviors and subjected to amphetamine, or ouabain administration for induction of manic-like behaviors. SB reversed the depressive-like and manic-like behaviors evaluated in the animal models. From these results we can suggest that SB may be a potential mood stabilizer.

Sodium butyrate and mood stabilizers block ouabain-induced hyperlocomotion and increase BDNF, NGF and GDNF levels in brain of Wistar rats

“…In the present study, as well as Li and VPA, SB reversed the ouabaininduced hyperactivity in rats. Indeed, in recent studies from our laboratory research it was reported that SB treatment prevented and reversed the manic-like behaviors induced by ouabain and Damphetamine (Arent et al, 2011;Moretti et al, 2011;Resende et al, 2013;Stertz et al, 2014;Valvassori et al, 2013;Steckert et al, 2013).…”

“…Note: The doses of drugs used in the present study were based in previous studies: ouabain from Riegel et al (2009), Li and VPA from Jornada et al (2010) and SB from Resende et al (2013).…”

“…It has been shown that VPA modulates the epigenetic programming by inhibiting histone deacetylases (HDAC) (Machado-Vieira et al, 2011). Recent preclinical studies from our research group showed that treatment with sodium butyrate (SB), an inhibitor of histone deacetylase like VPA, was able to reverse the manic-like behavior induced by amphetamine in rodents (Arent et al, 2011;Resende et al, 2013;Steckert et al, 2013;Valvassori et al, 2013).…”

Epigenetic approaches for bipolar disorder drug discovery

“…DNMT: DNA methyltransferase; HDAC: Histone deacetylase; NA: Not available. VPA, TSA HDACi Lymphocyte culture [60] VPA HDACi Cultured rat cortical neurons [74] MS-275 HDACi Mouse [106] Sodium butyrate HDACi Rat [75] Sodium butyrate HDACi Rat [107] Sodium butyrate HDACi Rat [108] Sodium butyrate HDACi Rat [109] Sodium butyrate HDACi Rat [110] Cpd-60 HDACi Mouse can cause mania when given to patients with MDD may give some insight into the pathophysiology of MDD and BD.…”

Challenges with bipolar disorder drug discovery

“…Ebselen, possibly acting as an inositol monophosphatase (IMPase) inhibitor, has exhibited lithium-like effects in both depression and mania preclinical models. [17] Two selective HDAC inhibitors, compound 60 (Cpd-60) [18] and sodium butyrate, [19] demonstrated reversal of depressive-like and manic-like behaviors in animal studies, and these behavioral changes were related with gene expression alteration, as confirmed by increased histone acetylation. Another interesting hypothesis based on preclinical data suggests that arachidonic acid (AA) cascade may be a candidate pathway for developing BD treatments.…”