Vannucci Susan J, Simpson Ian A
Department of Pediatrics, University, New York, New York 10032, USA.
Am J Physiol Endocrinol Metab. 2003 Nov;285(5):E1127-34. doi: 10.1152/ajpendo.00187.2003.
Normal development of both human and rat brain is associated with a switch in metabolic fuel from a combination of glucose and ketone bodies in the immature brain to a nearly total reliance on glucose in the adult. The delivery of glucose, lactate, and ketone bodies from the blood to the brain requires specific transporter proteins, glucose and monocarboxylic acid transporter proteins (GLUTs and MCTs), respectively. Developmental expression of the GLUTs in rat brain, i.e., 55-kDa GLUT1 in the blood-brain barrier (BBB), 45-kDa GLUT1 and GLUT3 in vascular-free brain, corresponds to maturational increases in cerebral glucose uptake and utilization. It has been suggested that MCT expression peaks during suckling and sharply declines thereafter, although a comparable detailed study has not been done. This study investigated the temporal and regional expression of MCT1 and MCT2 mRNA and protein in the BBB and the nonvascular brain during postnatal development in the rat. The results confirmed maximal MCT1 mRNA and protein expression in the BBB during suckling and a decline with maturation, coincident with the switch to glucose as the predominant cerebral fuel. However, nonvascular MCT1 and MCT2 levels do not reflect changes in cerebral energy metabolism, suggesting a more complex regulation. Although MCT1 assumes a predominantly glial expression in postweanling brain, the concentration remains fairly constant, as does that of MCT2 in neurons. The maintenance of nonvascular MCT levels in the adult brain implies a major role for these proteins, in concert with the GLUTs in both neurons and astrocytes, to transfer glycolytic intermediates during cerebral energy metabolism.
人类和大鼠大脑的正常发育都与代谢燃料的转换有关，从不成熟大脑中葡萄糖和酮体的组合，转变为成年后几乎完全依赖葡萄糖。葡萄糖、乳酸和酮体从血液输送到大脑分别需要特定的转运蛋白，即葡萄糖和单羧酸转运蛋白（GLUTs和MCTs）。大鼠大脑中GLUTs的发育表达，即血脑屏障（BBB）中的55-kDa GLUT1、无血管大脑中的45-kDa GLUT1和GLUT3，与大脑葡萄糖摄取和利用的成熟增加相对应。有人提出MCT表达在哺乳期间达到峰值，此后急剧下降，尽管尚未进行类似的详细研究。本研究调查了大鼠出生后发育过程中BBB和非血管性大脑中MCT1和MCT2 mRNA及蛋白的时间和区域表达。结果证实，BBB中MCT1 mRNA和蛋白表达在哺乳期间最高，随着成熟而下降，这与转变为以葡萄糖作为主要脑燃料的过程一致。然而，非血管性MCT1和MCT2水平并不能反映脑能量代谢的变化，表明其调控更为复杂。尽管断奶后大脑中MCT1主要在胶质细胞中表达，但其浓度保持相当恒定，神经元中的MCT2浓度也是如此。成人大脑中非血管性MCT水平的维持意味着这些蛋白质在神经元和星形胶质细胞中与GLUTs协同作用，在脑能量代谢过程中转移糖酵解中间产物方面发挥重要作用。
