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 hyp ertrophic processes which characterize reactive astrocytosis. We have investigated the possibility that ATP, an agent that is released by in jured 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 extracellula r ATP on properties associated with astrogliosis. Light microscopic st udies disclosed marked stellation of astrocytes after 30-60 min of exp osure to 100 mu M - 1 mM ATP. In addition, the content of the astrocyt e-specific intermediate filament, glial fibrillary acidic protein (GFA P), was increased 35-40 % following 60-min exposure to ATP; this effec t persisted for 1-3 days of exposure to 100 mu M ATP. [H-3]Thymidine i ncorporation increased progressively from 1-3 days; a 3.6-fold increas e in DNA synthesis was observed following 3 days of exposure to 1 mM A TP, suggesting stimulation of cellular proliferation. These findings s how that high micromolar to low millimolar concentrations of extracell ular ATP reproduce several features associated with reactive gliosis a nd suggest that extracellular ATP may be involved in the activation of astrocytes following CNS injury.