Extracellular ATP induces stellation and increases glial fibrillary acidic protein content and DNA synthesis in primary astrocyte cultures.

A number of factors appear to be involved in the proliferative and hypertrophic processes which characterize reactive astrocytosis. We have investigated the possibility that ATP, an agent that is released by injured cells following tissue destruction, may be one such factor. For this purpose, we utilized primary cultures of astrocytes derived from cerebral cortices of neonatal rats to study the effect of extracellular ATP on properties associated with astrogliosis. Light microscopic studies disclosed marked stellation of astrocytes after 30-60 min of exposure to 100 microM-1 mM ATP. In addition, the content of the astrocyte-specific intermediate filament, glial fibrillary acidic protein (GFAP), was increased 35-40% following 60-min exposure to ATP; this effect persisted for 1-3 days of exposure to 100 microM ATP. [3H]Thymidine incorporation increased progressively from 1-3 days; a 3.6-fold increase in DNA synthesis was observed following 3 days of exposure to 1 mM ATP, suggesting stimulation of cellular proliferation. These findings show that high micromolar to low millimolar concentrations of extracellular ATP reproduce several features associated with reactive gliosis and suggest that extracellular ATP may be involved in the activation of astrocytes following CNS injury.