Synergistic Effects of Sodium Butyrate, a Histone Deacetylase Inhibitor, on Increase of Neurogenesis Induced by Pyridoxine and Increase of Neural Proliferation in the Mouse Dentate Gyrus

Abstract

We previously observed that pyridoxine (vitamin B(6)) significantly increased cell proliferation and neuroblast differentiation without any neuronal damage in the hippocampus. In this study, we investigated the effects of sodium butyrate, a histone deacetylase (HDAC) inhibitor which serves as an epigenetic regulator of gene expression, on pyridoxine-induced neural proliferation and neurogenesis induced by the increase of neural proliferation in the mouse dentate gyrus. Sodium butyrate (300 mg/kg, subcutaneously), pyridoxine (350 mg/kg, intraperitoneally), or combination with sodium butyrate were administered to 8-week-old mice twice a day and once a day, respectively, for 14 days. The administration of sodium butyrate significantly increased acetyl-histone H3 levels in the dentate gyrus. Sodium butyrate alone did not show the significant increase of cell proliferation in the dentate gyrus. But, pyridoxine alone significantly increased cell proliferation. Sodium butyrate in combination with pyridoxine robustly enhanced cell proliferation and neurogenesis induced by the increase of neural proliferation in the dentate gyrus, showing that sodium butyrate treatment distinctively enhanced development of neuroblast dendrites. These results indicate that an inhibition of HDAC synergistically promotes neurogenesis induced by a pyridoxine and increase of neural proliferation.

Combination Effects of Sodium Butyrate and Pyridoxine Treatment on Cell Proliferation and Neuroblast Differentiation in the Dentate Gyrus of d-Galactose-Induced Aging Model Mice

“…g The mean number of DCXimmunoreactive neuroblasts with and without tertiary dendrites per section in all the groups (n = 7 per group; *P \ 0.05, indicating a significant difference compared to the control group; # P \ 0.05, significantly different from the D-gal-vehicle group). The bars indicate the SEM administered adult mice significantly increased cell proliferation and neuroblast differentiation in the dentate gyrus [27].…”

“…In addition, we found that sodium butyrate (SB), a histone deacetylase (HDAC) inhibitor, robustly increased Pyr-induced cell proliferation and neuroblast differentiation in the mouse dentate gyrus [27]. In the present study, we investigated whether the stimulation of neurogenesis in the brain might yield benefits for cerebral dysfunctions that are associated with the aging induced by D-gal.…”

Cross Talk Between the Notch Signaling and Noncoding RNA on the Fate of Stem Cells

“…Histone deacetylases (HDACs) are a class of enzymes that remove the acetyl group from the N-terminal tails of histones and alter their interaction with DNA, thus serving as epigenetic regulators of gene expression. 35 Based on the structural characteristics of HDACs, the HDAC family of proteins are grouped into classes I, II, and IV. 36 Class I HDACs, including HDAC1, HDAC2, HDAC3, and HDAC8, have ubiquitous tissue distribution and present within the cell nucleus.…”

Epigenetic stability in the adult mouse cortex under conditions of pharmacologically induced histone acetylation

“…In particular, epigenetic modification by histone acetylases (HATs) and deacetylases (HDACs) appears to modulate the dynamic gene expression which underlies synaptic plasticity (Stefanko et al 2009; Kavalali et al 2011) as well as learning and memory (Haettig et al 2011). Histone acetylation has also been considered to be critical for brain development; e.g., it has been shown to have large effects on cell proliferation (Umka et al 2010; Yoo et al 2011), migration (Nott et al 2013), and synapse formation/maturation (Akhtar et al 2009). Indeed, there seems to be few cellular processes which have not been assigned a relation to histone acetylation.…”