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Transcriptional therapy with the histone deacetylase inhibitor trichostatin A ameliorates experimental autoimmune encephalomyelitis.
- Source :
-
Journal of neuroimmunology [J Neuroimmunol] 2005 Jul; Vol. 164 (1-2), pp. 10-21. - Publication Year :
- 2005
-
Abstract
- 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.
- Subjects :
- Animals
Cell Death drug effects
Cells, Cultured
Cerebral Cortex cytology
Cytokines genetics
Cytokines metabolism
Disease Models, Animal
Drug Administration Schedule
Drug Interactions
Embryo, Mammalian
Encephalomyelitis, Autoimmune, Experimental chemically induced
Encephalomyelitis, Autoimmune, Experimental genetics
Encephalomyelitis, Autoimmune, Experimental pathology
Female
Gene Expression Profiling methods
Glycoproteins
Immunohistochemistry methods
Mice
Mice, Inbred C57BL
Myelin-Oligodendrocyte Glycoprotein
Neurons drug effects
Oligonucleotide Array Sequence Analysis methods
Peptide Fragments
RNA, Messenger metabolism
Rats
Rats, Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction methods
Severity of Illness Index
Spleen drug effects
Spleen metabolism
Tetrazolium Salts
Thiazoles
Time Factors
Encephalomyelitis, Autoimmune, Experimental drug therapy
Gene Expression Regulation drug effects
Hydroxamic Acids therapeutic use
Protein Synthesis Inhibitors therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 0165-5728
- Volume :
- 164
- Issue :
- 1-2
- Database :
- MEDLINE
- Journal :
- Journal of neuroimmunology
- Publication Type :
- Academic Journal
- Accession number :
- 15885809
- Full Text :
- https://doi.org/10.1016/j.jneuroim.2005.02.022