Novel growth factor Gas6, phosphatidylserine and their age-related changesin the rat brain.

Gas6 is the newest member of the family of vitamin K-dependent proteins tha t acts as a ligand for the Axl family of RTK with homology to neural cell a dhesion molecules. Gas6-Axl interactions have been implicated in anti-apopt otic activity. Here we report the first identification of Gas6 in the rat b rain synaptosomes from three brain regions: striatum, hippocampus and front al cortex. Furthermore, we discovered age-related and area-specific decline s 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 dra matic decrease in Gas6 with aging lover 84% decline in old animals, as comp ared with young) (p<0.001). Gas6 levels in synaptosomes derived from striat um 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 c ortex, 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 chan ges in distinct neuronal population viability. Thus, our findings suggest f or the first time a role for Gas6 in brain aging.