Transcriptional regulation of brain derived neurotrophic factor (BDNF) by methyl CpG binding protein 2 (MeCP2): implication in re-myelination and/or myelin repair in an animal model of multiple sclerosis (MS)

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Khorshid Ahmad, Tina Jr
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Multiple sclerosis (MS) is a chronic neurological disease characterized by the destruction of central nervous system (CNS) myelin. Although the neurotrophin, brain derived neurotrophic factor (BDNF) has a beneficial role in re-myelination and/or myelin repair, these effects are hampered by the over-expression of a transcriptional repressor isoform of methyl CpG binding protein 2 (MeCP2) called MeCP2E1. We hypothesize that following experimental autoimmune encephalomyelitis (EAE) -induced myelin damage, the immune system induction of the pathogenic MeCP2E1 isoform hampers the re-myelination and/or myelin repair process by repressing BDNF expression. Our research identified the temporal gene and protein expression changes of MeCP2E1, MeCP2E2 and BDNF in an EAE mouse model of MS, and correlated them with the changes in the neurological disability scores (NDS). Our results indicated MeCP2E1 mRNA levels are elevated in EAE animals which is responsible for the repressed BDNF production in the spinal cord that prevents re-myelination and/or myelin repair.
Multiple sclerosis (MS), Experimental autoimmune encephalomyelitis (EAE), Methyl CpG binding protein 2 (MeCP2), Brain-derived neurotrophic factor (BDNF), Neurological disability scoring (NDS), Myelin repair
KhorshidAhmad, T., et al., Transcriptional Regulation of Brain-Derived Neurotrophic Factor (BDNF) by Methyl CpG Binding Protein 2 (MeCP2): a Novel Mechanism for Re-Myelination and/or Myelin Repair Involved in the Treatment of Multiple Sclerosis (MS). Mol Neurobiol, 2015.