Developmental switch in brain nutrient transporter expression in the rat
Developmental switch in brain nutrient transporter expression in the rat
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DOI：
10.1152/ajpendo.00187.2003
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发表时间：
2003-11-01
影响因子：
5.1
通讯作者：
Simpson, IA
中科院分区：
文献类型：
--
作者：
Vannucci, SJ;Simpson, IA
人类和大鼠大脑的正常发育与代谢燃料的转换有关，在未成熟的大脑中，代谢燃料从葡萄糖和酮体的组合转变为成年人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需要特定的转运蛋白、葡萄糖和单羧酸转运蛋白(GLUT和MCTs)。Gluts在大鼠脑内的发育表达，即血脑屏障(BBB)中的55 kDa GLUT1，无血管脑中的45 kDa GLUT1和GLUT3，对应于大脑葡萄糖摄取和利用的成熟增加。有人认为，MCT的表达在哺乳期间达到顶峰，之后急剧下降，尽管还没有进行类似的详细研究。本研究探讨了MCT1和MCT2在大鼠出生后发育过程中血脑屏障和非血管脑组织中MCT1和MCT2基因和蛋白的表达。结果证实，在哺乳期间，血脑屏障中MCT1mRNA和蛋白的表达最高，随着发育成熟，MCT1mRNA和蛋白的表达下降，这与以葡萄糖为主要脑燃料的转变相一致。然而，非血管MCT1和MCT2水平不能反映大脑能量代谢的变化，这表明一种更复杂的调节。虽然MCT1在断奶后的大脑中主要以神经胶质细胞表达，但其浓度保持相当稳定，神经元中的MCT2也是如此。成人大脑中非血管MCT水平的维持意味着这些蛋白在大脑能量代谢过程中与神经元和星形胶质细胞中的谷氨酸协同传递糖酵解中间产物的主要作用。
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.