Neuronal differentiation is triggered by oleic acid synthesized and released by astrocytes

Unlike in the adult brain, the newborn brain specifically takes up serum al bumin during the postnatal period, coinciding with the stage of maximal bra in development. Here we report that albumin stimulates oleic acid synthesis by astrocytes from the main metabolic substrates available during brain de velopment. Oleic acid released by astrocytes is used by neurons for the syn thesis of phospholipids and is specifically incorporated into growth cones. Oleic acid promotes axonal growth, neuronal clustering, and expression of the axonal growth-associated protein-43, GAP-43; all these observations ind icating neuronal differentiation. The effect of oleic acid on GAP-43 synthe sis is brought about by the activation of protein kinase C, since it was pr evented by inhibitors of this kinase, such as H-7, polymyxin or sphingosine . The expression of GAP-43 was significantly increased in neurons co-cultur ed with astrocytes by the presence of albumin indicating that neuronal diff erentiation takes place in the presence of oleic acid synthesized and relea sed by astrocytes in situ. In conclusion, during brain development the pres ence of albumin could play an important role by triggering the synthesis an d release of oleic acid by astrocytes, which induces neuronal differentiati on.