Tabernero A, Lavado E M, Granda B, Velasco A, Medina J M
Unidad de Investigación, Hospital Universitario de Salamanca, Spain.
J Neurochem. 2001 Nov;79(3):606-16. doi: 10.1046/j.1471-4159.2001.00598.x.
Unlike in the adult brain, the newborn brain specifically takes up serum albumin during the postnatal period, coinciding with the stage of maximal brain development. Here we report that albumin stimulates oleic acid synthesis by astrocytes from the main metabolic substrates available during brain development. Oleic acid released by astrocytes is used by neurons for the synthesis 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 indicating neuronal differentiation. The effect of oleic acid on GAP-43 synthesis is brought about by the activation of protein kinase C, since it was prevented by inhibitors of this kinase, such as H-7, polymyxin or sphingosine. The expression of GAP-43 was significantly increased in neurons co-cultured with astrocytes by the presence of albumin indicating that neuronal differentiation takes place in the presence of oleic acid synthesized and released by astrocytes in situ. In conclusion, during brain development the presence of albumin could play an important role by triggering the synthesis and release of oleic acid by astrocytes, which induces neuronal differentiation.
与成人大脑不同,新生大脑在出生后特定时期会摄取血清白蛋白,这与大脑发育的高峰期相吻合。我们在此报告,白蛋白可刺激星形胶质细胞利用大脑发育期间可用的主要代谢底物合成油酸。星形胶质细胞释放的油酸被神经元用于合成磷脂,并特异性地整合到生长锥中。油酸促进轴突生长、神经元聚集以及轴突生长相关蛋白43(GAP - 43)的表达;所有这些观察结果均表明神经元分化。油酸对GAP - 43合成的影响是由蛋白激酶C的激活引起的,因为这种激酶的抑制剂(如H - 7、多粘菌素或鞘氨醇)可阻止这种影响。在与星形胶质细胞共培养的神经元中,白蛋白的存在显著增加了GAP - 43的表达,这表明神经元分化发生在星形胶质细胞原位合成并释放的油酸存在的情况下。总之,在大脑发育过程中,白蛋白的存在可能通过触发星形胶质细胞合成和释放油酸来发挥重要作用,而油酸可诱导神经元分化。