MeCP2 deficiency enhances glutamate release through NF-κB signaling in myeloid derived cells

The signaling pathway involved in regulating glutamate release was investigated. Glutaminase mRNA levels were higher in microglia isolated from mice treated with lipopolysaccharide. Pam3CSK and lipopolysaccharide stimulated glutamate release in neonatal mouse microglia cultures, which was attenuated by NF-kappa B inhibitors. Higher levels of glutaminase mRNA and glutamate release were observed in human peripheral blood mononuclear cells made MeCP2 deficient with MeCP2 shRNA, which was blocked by NF-kappa B inhibitors. NF-kappa B inhibitors also decreased the higher levels of glutaminase mRNA in MeCP2 deficient THP1 monocyte cell lines. Finally, an inverse relation was observed between MeCP2 levels and NF-kappa B reporter activity in THP1 cells. We suggest that NF-kappa B pathway is involved in the release of glutamate in MeCP2 deficient cells from the myeloid lineage. (C) 2013 Elsevier B.V. All rights reserved.