PMID- 19360904 OWN - NLM STAT- MEDLINE DCOM- 20090921 LR - 20131121 IS - 1097-4547 (Electronic) IS - 0360-4012 (Linking) VI - 87 IP - 11 DP - 2009 Aug 15 TI - Histone deacetylase inhibitors promote neurosteroid-mediated cell differentiation and enhance serotonin-stimulated brain-derived neurotrophic factor gene expression in rat C6 glioma cells. PG - 2608-14 LID - 10.1002/jnr.22072 [doi] AB - Progesterone treatment has previously been reported to promote the differentiation of glial cells probably through the production of 5alpha-reduced neurosteroids, resulting in the enhancement of serotonin-stimulated brain-derived neurotrophic factor (BDNF) gene expression, which is considered to contribute to the survival, regeneration, and plasticity of neuronal cells in the brain and hence has been suggested to improve mood disorders and other symptoms in depressive patients. Based on these previous observations, the effects on glial cells of histone deacetylase (HDAC) inhibitors, which are known as agents promoting cell differentiation, were examined using rat C6 glioma cells as a model for in vitro studies. Consequently, trichostatin A (TSA), sodium butyrate (NaB), and valproic acid (VPA) stimulated glial fibrillary acidic protein (GFAP) gene expression, and their stimulatory effects on GFAP gene expression were inhibited by treatment of these cells with finasteride, an inhibitor of the enzyme producing 5alpha-reduced neurosteroids. In addition, HDAC inhibitors enhanced serotonin-stimulated BDNF gene expression, the enhancement of which could be abolished by the inhibition of 5alpha-reduced neurosteroid production in the glioma cells. These results suggest that HDAC inhibitors may be able to promote the differentiation of rat C6 glioma cells through the production of 5alpha-reduced neurosteroids, resulting in the enhancement of serotonin-stimulated BDNF gene expression as a consequence of promoting their differentiation, indicating the possibility that differentiated glial cells may be implicated in preserving the integrity of neural networks as well as improving the function of neuronal cells in the brain. FAU - Morita, Kyoji AU - Morita K AD - Laboratory of Neuropharmacology, Department of Nursing, Shikoku University School of Health Sciences, Ohjin, Tokushima, Japan. kmorita@shikoku-u.ac.jp FAU - Gotohda, Takako AU - Gotohda T FAU - Arimochi, Hideki AU - Arimochi H FAU - Lee, Mi-Sook AU - Lee MS FAU - Her, Song AU - Her S LA - eng PT - Journal Article PL - United States TA - J Neurosci Res JT - Journal of neuroscience research JID - 7600111 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Butyrates) RN - 0 (Enzyme Inhibitors) RN - 0 (Glial Fibrillary Acidic Protein) RN - 0 (Histone Deacetylase Inhibitors) RN - 0 (Hydroxamic Acids) RN - 0 (RNA, Messenger) RN - 0 (Sodium Compounds) RN - 0 (Steroids) RN - 333DO1RDJY (Serotonin) RN - 3X2S926L3Z (trichostatin A) RN - 57GNO57U7G (Finasteride) RN - 614OI1Z5WI (Valproic Acid) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*genetics/metabolism MH - Butyrates/pharmacology MH - Cell Differentiation/*drug effects/physiology MH - Cell Line, Tumor MH - Dose-Response Relationship, Drug MH - Enzyme Inhibitors/pharmacology MH - Finasteride/pharmacology MH - Gene Expression/*drug effects MH - Glial Fibrillary Acidic Protein/*genetics/metabolism MH - *Histone Deacetylase Inhibitors MH - Hydroxamic Acids/pharmacology MH - Neuroglia/*drug effects/metabolism MH - RNA, Messenger/metabolism MH - Rats MH - Serotonin/metabolism MH - Sodium Compounds/pharmacology MH - Steroids/metabolism MH - Time Factors MH - Valproic Acid/pharmacology EDAT- 2009/04/11 09:00 MHDA- 2009/09/22 06:00 CRDT- 2009/04/11 09:00 PHST- 2009/04/11 09:00 [entrez] PHST- 2009/04/11 09:00 [pubmed] PHST- 2009/09/22 06:00 [medline] AID - 10.1002/jnr.22072 [doi] PST - ppublish SO - J Neurosci Res. 2009 Aug 15;87(11):2608-14. doi: 10.1002/jnr.22072.