Glial soluble factors regulate the activity and expression of the neuronal glutamate transporter EAAC1: implication of cholesterol
Version of Record online: 27 JAN 2004
Journal of Neurochemistry
Volume 88, Issue 6, pages 1521–1532, March 2004
How to Cite
Canolle, B., Masmejean, F., Melon, C., Nieoullon, A., Pisano, P. and Lortet, S. (2004), Glial soluble factors regulate the activity and expression of the neuronal glutamate transporter EAAC1: implication of cholesterol. Journal of Neurochemistry, 88: 1521–1532. doi: 10.1046/j.1471-4159.2003.02301.x
- Issue online: 20 FEB 2004
- Version of Record online: 27 JAN 2004
- Resubmitted manuscript received October 10, 2003; accepted November 20, 2003.
- glial soluble factors;
- glutamate transport;
- pure neuronal culture
A co-ordinated regulation between neurons and astrocytes is essential for the control of extracellular glutamate concentration. Here, we have investigated the influence of astrocytes and glia-derived cholesterol on the regulation of glutamate transport in primary neuronal cultures from rat embryonic cortices. Glutamate uptake rate and expression of the neuronal glutamate transporter EAAC1 were low when neurons were grown without astrocytes and neurons were unable to clear extracellular glutamate. Treatment of the neuronal cultures with glial conditioned medium (GCM) increased glutamate uptake Vmax, EAAC1 expression and restored the capacity of neurons to eliminate extracellular glutamate. Thus, astrocytes up-regulate the activity and expression of EAAC1 in neurons. We further showed that cholesterol, present in GCM, increased glutamate uptake activity when added directly to neurons and had no effect on glutamate transporter expression. Furthermore, part of the GCM-induced effect on glutamate transport activity was lost when cholesterol was removed from GCM (low cholesterol-GCM) and was restored when cholesterol was added to low cholesterol-GCM. This demonstrates that glia-derived cholesterol regulates glutamate transport activity. With these experiments, we provide new evidences for neuronal glutamate transport regulation by astrocytes and identified cholesterol as one of the factors implicated in this regulation.