Glial activation modulates glutamate neurotoxicity in cerebellar granule cell cultures.
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.
Pérez-Capote
Kamil
K
Department of Pharmacology and Toxicology, Institut d'Investigacions Biomèdiques de Barcelona-Consejo Superior de Investigaciones Cientificas (CSIC), Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
Serratosa
Joan
J
Solà
Carme
C
D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000633:toxicity*; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D018698:Glutamic Acid