Role of oleic acid as a neurotrophic factor is supported in vivo by the expression of GAP-43 subsequent to the activation of SREBP-1 and the up-regulation of stearoyl-CoA desaturase during postnatal development of the brain

We have recently reported that albumin, a serum protein present in the developing brain, stimulates the synthesis of oleic acid by cultured astrocytes by inducing stearoyl-CoA 9-desaturase, the rate-limiting enzyme in oleic acid synthesis, through activation of the sterol regulatory element-binding protein-1. In this work, we offer evidence supporting the in vivo occurrence of this process during the postnatal development of the rat brain. Our results show that albumin reaches maximal brain level by day 1 after birth, coinciding with activation of the sterol response element binding protein-1, which is responsible for the transcription of the enzymes required for oleic acid synthesis. In addition, the developmental profile of stearoyl-CoA 9-desaturase-1 mRNA expression follows that of sterol regulatory element-binding protein-1 activation, indicating that these phenomena are tightly linked. In a previous work, we showed that oleic acid induces neuronal differentiation, as indicated by the expression of growth associated protein-43. Here, we report that the expression of growth associated protein-43 mRNA peaks at about day 7 after birth, following the maximal expression of stearoyl-CoA 9-desaturase-1 mRNA that occurs between days 3 and 5 postnatally. In conclusion, our results support the hypothesis that the synthesis of oleic acid is linked to neuronal differentiation during rat brain development. (C) 2003 Elsevier Science B.V. All rights reserved.