Department of Nutrition, Food Science and Physiology, University of Navarra, Irunlarrea 1, 31008, Pamplona, Spain.
Nutrition Research Centre, University of Navarra, Pamplona, Spain.
Mol Neurobiol. 2020 Feb;57(2):798-805. doi: 10.1007/s12035-019-01743-1. Epub 2019 Aug 31.
The brain depends on glucose as a source of energy. This implies the presence of glucose transporters, being GLUT1 and GLUT3 the most relevant. Expression of GLUT12 is found in mouse and human brain at low levels. We previously demonstrated GLUT12 upregulation in the frontal cortex of aged subjects that was even higher in aged Alzheimer's disease (AD) patients. However, the cause and the mechanism through which this increase occurs are still unknown. Here, we aimed to investigate whether the upregulation of GLUT12 in AD is related with aging or Aβ deposition in comparison with GLUT1, GLUT3, and GLUT4. In the frontal cortex of two amyloidogenic mouse models (Tg2576 and APP/PS1) GLUT12 levels were increased. Contrary, expression of GLUT1 and GLUT3 were decreased, while GLUT4 did not change. In aged mice and the senescence-accelerated model SAMP8, GLUT12 and GLUT4 were upregulated in comparison with young animals. GLUT1 and GLUT3 did not show significant changes with age. The effect of β-amyloid (Aβ) deposition was also evaluated in Aβ peptide i.c.v. injected mice. In the hippocampus, GLUT12 expression increased whereas GLUT4 was not modified. Consistent with the results in the amyloidogenic models, GLUT3 and GLUT1 were downregulated. In summary, Aβ increases GLUT12 protein expression in the brain pointing out a central role of the transporter in AD pathology and opening new perspectives for the treatment of this neurodegenerative disease.
大脑依赖葡萄糖作为能量来源。这意味着存在葡萄糖转运蛋白，其中 GLUT1 和 GLUT3 最为重要。在小鼠和人脑中，GLUT12 的表达水平较低。我们之前证明，在老年受试者的额皮质中 GLUT12 上调，而在老年阿尔茨海默病（AD）患者中甚至更高。然而，这种增加发生的原因和机制仍不清楚。在这里，我们旨在研究 AD 中 GLUT12 的上调是否与衰老或 Aβ沉积有关，与 GLUT1、GLUT3 和 GLUT4 相比。在两种淀粉样蛋白模型（Tg2576 和 APP/PS1）的额皮质中，GLUT12 水平增加。相反，GLUT1 和 GLUT3 的表达减少，而 GLUT4 没有变化。在老年小鼠和加速衰老模型 SAMP8 中，与年轻动物相比，GLUT12 和 GLUT4 上调。GLUT1 和 GLUT3 随年龄变化不显著。还评估了β-淀粉样蛋白（Aβ）沉积对 i.c.v. 注射 Aβ 肽的小鼠的影响。在海马体中，GLUT12 表达增加，而 GLUT4 没有改变。与淀粉样蛋白模型的结果一致，GLUT3 和 GLUT1 下调。总之，Aβ增加了大脑中 GLUT12 蛋白的表达，指出了该转运蛋白在 AD 病理学中的核心作用，并为治疗这种神经退行性疾病开辟了新的前景。
