Glial activation modulates glutamate neurotoxicity in cerebellar granule cell cultures
Version of Record online: 11 DEC 2003
Copyright © 2003 Wiley-Liss, Inc.
Volume 45, Issue 3, pages 258–268, February 2004
How to Cite
Pérez-Capote, K., Serratosa, J. and Solà, C. (2004), Glial activation modulates glutamate neurotoxicity in cerebellar granule cell cultures. Glia, 45: 258–268. doi: 10.1002/glia.10329
- Issue online: 3 JAN 2004
- Version of Record online: 11 DEC 2003
- Manuscript Accepted: 25 AUG 2003
- Manuscript Received: 17 JUL 2003
- Ministerio de Ciencia y Tecnología. Grant Number: SAF 2001-2240
- Instituto Carlos III
- CIEN network
- Institut d'Investigacions Biomèdiques August Pi i Sunyer
- reactive glial cells;
We studied the influence of glial cells on the neuronal response to glutamate toxicity in cerebellar granule cell cultures. We compared the effect of glutamate on neuronal viability in neuronal vs. neuronal-glial cultures and determined this effect after pretreating the cultures with the lipopolysaccharide (LPS) of Escherichia coli, agent widely used to induce glial activation. Morphological changes in glial cells and nitric oxide (NO) production were evaluated as indicators of glial activation. We observed that glutamate neurotoxicity in neuronal-glial cultures was attenuated in a certain range of glutamate concentration when compared to neuronal cultures, but it was enhanced at higher glutamate concentrations. This enhanced neurotoxicity was associated with morphological changes in astrocytes and microglial cells in the absence of NO production. LPS treatment induced morphological changes in glial cells in neuronal-glial cultures as well as NO production. These effects occurred in the absence of significant neuronal death. However, when LPS-pretreated cultures were treated with glutamate, the sensitivity of neuronal-glial cultures to glutamate neurotoxicity was increased. This was accompanied by additional morphological changes in glial cells in the absence of a further increase in NO production. These results suggest that quiescent glial cells protect neuronal cells from glutamate neurotoxicity, but reactive glial cells increase glutamate neurotoxicity. Therefore, glial cells play a key role in the neuronal response to a negative stimulus, suggesting that this response can be modified through an action on glial cells. © 2003 Wiley-Liss, Inc.