von Leden Ramona E, Moritz Kasey E, Bermudez Sara, Jaiswal Shalini, Wilson Colin M, Dardzinski Bernard J, Byrnes Kimberly R
Neuroscience Program, Uniformed Services University, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA.
Department of Anatomy, Physiology, and Genetics, Uniformed Services University, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA.
Neurosci Lett. 2019 Jan 18;690:23-28. doi: 10.1016/j.neulet.2018.10.004. Epub 2018 Oct 6.
Aging results in increased activation of inflammatory glial cells and decreased neuronal viability following spinal cord injury (SCI). Metabolism and transport of glucose is also decreased with age, although the influence of age on glucose transporter (GLUT) expression or glucose uptake in SCI is currently unknown. We therefore performed [F]Fluorodeoxyglucose (FDG) PET imaging of young (3 month) and middle-aged (12 month) rats. Glucose uptake in middle-aged rats was decreased compared to young rats at baseline, followed by increased uptake 14 days post contusion SCI. qRT-PCR and protein analysis revealed an association between 14 day glucose uptake and 14 day post-injury inflammation. Further, gene expression analysis of neuron-specific GLUT3 and non-specific GLUT4 (present on glial cells) revealed an inverse relationship between GLUT3/4 gene expression and glucose uptake patterns. Protein expression revealed increased GLUT3 in 3 month rats only, consistent with age related decreases in glucose uptake, and increased GLUT4 in 12 month rats only, consistent with age related increases in inflammatory activity and glucose uptake. Inconsistencies between gene and protein suggest an influence of age-related impairment of translation and/or protein degradation. Overall, our findings show that age alters glucose uptake and GLUT3/4 expression profiles before and after SCI, which may be dependent on level of inflammatory response, and may suggest a therapeutic avenue in addressing glucose uptake in the aging population.
衰老导致脊髓损伤（SCI）后炎症性胶质细胞的激活增加和神经元活力下降。随着年龄的增长，葡萄糖的代谢和转运也会减少，尽管目前尚不清楚年龄对SCI中葡萄糖转运蛋白（GLUT）表达或葡萄糖摄取的影响。因此，我们对年轻（3个月）和中年（12个月）大鼠进行了[F]氟脱氧葡萄糖（FDG）PET成像。与年轻大鼠相比，中年大鼠在基线时的葡萄糖摄取减少，随后在挫伤性SCI后14天摄取增加。qRT-PCR和蛋白质分析显示14天的葡萄糖摄取与损伤后14天的炎症之间存在关联。此外，对神经元特异性GLUT3和非特异性GLUT4（存在于胶质细胞上）的基因表达分析揭示了GLUT3/4基因表达与葡萄糖摄取模式之间的负相关关系。蛋白质表达显示仅在3个月大的大鼠中GLUT3增加，这与年龄相关的葡萄糖摄取减少一致，并且仅在12个月大的大鼠中GLUT4增加，这与年龄相关的炎症活性和葡萄糖摄取增加一致。基因和蛋白质之间的不一致表明年龄相关的翻译和/或蛋白质降解受损的影响。总体而言，我们的研究结果表明，年龄会改变SCI前后的葡萄糖摄取和GLUT3/4表达谱，这可能取决于炎症反应水平，并且可能提示了一条解决老年人群葡萄糖摄取问题的治疗途径。
