6533b826fe1ef96bd1283a65

RESEARCH PRODUCT

The role of NG2 and OPC in induction and development of CNS inflammation

subject

description

encephalitis (EAE) mouse models (J Neurosci 31:669, 2011; Brain 136:1760, 2013). Further, it has been shown that in addition to infiltrating leukocytes, astrocytes and microglia also exhibit high expression of EMMPRIN in diseased brain. EMMPRIN has been reported to interact with monocarboxylate transporter-1 (MCT-1) in astrocytes; the lattermediates lactate transport to neurons. Given that perturbation in energymetabolism can have catastrophic effects on homeostasis of the brain, it is paramount to understand EMMPRIN expression in astrocytes in normal andMS brain.We have used human fetal astrocytes (HFA) and determined their EMMPRIN levels by flow cytometry and microscopy. We found that HFA in culture express high levels of EMMPRIN on their surface and that this was not readily altered by cytokine treatment. In contrast to cell surface EMMPRIN, soluble EMMPRIN (a 22 kDa fragment) was detected in low amounts in culture supernatants of HFA. Currently, we are using EMMPRIN specific siRNA to knockdown its expression on astrocytes and examine phenotypes including cellular integrity, MCT-1 expression and lactate metabolism in HFA, and support of neuronal survival in co-cultures. Also, using different pathway specific inhibitors we are investigating the mechanisms responsible for constitutive expression of EMMPRIN in HFA. The high EMMPRIN expression on astrocytes likely mediates important homeostatic functions that remain to be defined.