Novel growth factor Gas6, phosphatidylserine and their age-related changes in the rat brain

Gas6 is the newest member of the family of vitamin K-dependent proteins that acts as a ligand for the Axl family of RTK with homology to neural cell adhesion molecules. Gas6-Axl interactions have been implicated in anti- apoptotic activity. Here we report the first identification of Gas6 in the rat brain synaptosomes from three brain regions: striatum, hippocampus and frontal cortex. Furthermore, we discovered age-related and area-specific declines in the levels of Gas6 in the synaptosomes. The age effects on Gas6 levels were observed in all brain areas. Frontal cortex demonstrated the most dramatic decrease in Gas6 with aging (over 84% decline in old animals, as compared with young) (p < 0.001). Gas6 levels in synaptosomes derived from striatum and hippocampus of the old animals were over 55% lower than those of the young (p < 0.01). Phospholipid analysis of synaptosomes showed that in the cortex, decreases in Gas6 levels may be explained by age-related decrease in membrane phosphatidylserine composition. The brain area-specific decreases in Gas6 may in turn affect the RTK-regulated cell cycle, resulting in changes in distinct neuronal population viability. Thus, our findings suggest for the first time a role for Gas6 in brain aging.