Transcriptional therapy with the histone deacetylase inhibitor trichostatin A ameliorates experimental autoimmune encephalomyelitis

• DOI: 10.1016/j.jneuroim.2005.02.022
• Publication Date: 2005-05-11T11:51:09Z
• Authors: Sandra Camelo; Antonio H. Iglesias; Daehee Hwang; Brice Due; Hoon Ryu; Karen Smith; Steven G. Gray; Jaime Imitola; German Duran; Basel Assaf; Brett Langley; Samia J. Khoury; George Stephanopo...; Umberto De Girolami; Rajiv R. Ratan; Robert J. Ferrante; Fernando Dangond
• Keywords: Trichostatin A; Histone deacetylase inhibitor; Excitotoxicity; HDAC11; Histone deacetylase 5; Histone deacetylase 2

We demonstrate that the histone deacetylase (HDAC) inhibitor drug trichostatin A (TSA) reduces spinal cord inflammation, demyelination, neuronal and axonal loss and ameliorates disability in the relapsing phase of experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). TSA up-regulates antioxidant, anti-excitotoxicity and pro-neuronal growth and differentiation mRNAs. TSA also inhibits caspase activation and down-regulates gene targets of the pro-apoptotic E2F transcription factor pathway. In splenocytes, TSA reduces chemotactic, pro-Th1 and pro-proliferative mRNAs. A transcriptional imbalance in MS may contribute to immune dysregulation and neurodegeneration, and we identify HDAC inhibition as a transcriptional intervention to ameliorate this imbalance.