[Activation and cell death of astrocytes]

The mechanism of induction of reactive astrocytes (activation of astrocytes) that is observed in brain pathological conditions is not fully elucidated, and there is little information on the cell death of astrocytes. This mini-review summarizes our studies on the activation and cell death of astrocytes. Microinjection of endothelin-3 or the endothelinB-receptor agonist ala1,3,11,15-endothelin-1 enhanced the injury-induced increase in glial fibrillary acidic protein staining in rat neostriatum. Under these conditions, the receptor agonist did not affect the number of microglia/macrophage. The findings suggest that the signal cascade via endothelinB receptors in astrocytes is involved in induction of reactive astrocytes. We also found that Ca2+ depletion followed by reperfusion with Ca(2+)-containing medium caused cell death in cultured astrocytes (Ca2+ paradox-like injury). The study, carried out by the use of a specific antisense oligomer, provides direct evidence that Ca2+ paradox-like injury is mediated by the Na(+)-Ca2+ exchanger in the reverse mode. The injury was prevented by inhibitors of the Na(+)-Ca2+ exchanger and heat shock protein. Heat shock protein may affect processes downstream of the increase in intracellular Ca2+ concentration. Further studies on activation and cell injury of astrocytes will contribute to the development of new drugs that modulate the function of astrocytes.