Parkinson Gemma M, Dayas Christopher V, Smith Doug W
Neurobiology of Aging and Dementia Laboratory, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia; Preclinical Neurobiology Research Program, Centre for Brain and Mental Health Research, University of Newcastle, Callaghan, New South Wales, Australia; Hunter Medical Research Institute, New South Wales, Australia.
Preclinical Neurobiology Research Program, Centre for Brain and Mental Health Research, University of Newcastle, Callaghan, New South Wales, Australia; Hunter Medical Research Institute, New South Wales, Australia.
Neurobiol Aging. 2016 Sep;45:123-135. doi: 10.1016/j.neurobiolaging.2016.05.017. Epub 2016 May 24.
The spinal cord is vital for the processing of sensorimotor information and for its propagation to and from both the brain and the periphery. Spinal cord function is affected by aging, however, the mechanisms involved are not well-understood. To characterize molecular mechanisms of spinal cord aging, microarray analyses of gene expression were performed on cervical spinal cords of aging rats. Of the metabolic and signaling pathways affected, cholesterol-associated pathways were the most comprehensively altered, including significant downregulation of cholesterol synthesis-related genes and upregulation of cholesterol transport and metabolism genes. Paradoxically, a significant increase in total cholesterol content was observed-likely associated with cholesterol ester accumulation. To investigate potential mechanisms for the perturbed cholesterol homeostasis, we quantified the expression of myelin and neuroinflammation-associated genes and proteins. Although there was minimal change in myelin-related expression, there was an increase in phagocytic microglial and astrogliosis markers, particularly in the white matter. Together, these results suggest that perturbed cholesterol homeostasis, possibly as a result of increased inflammatory activation in spinal cord white matter, may contribute to impaired spinal cord function with aging.
脊髓对于感觉运动信息的处理以及该信息在大脑和外周之间的传递至关重要。然而，衰老会影响脊髓功能，但其涉及的机制尚未完全明确。为了表征脊髓衰老的分子机制，对老年大鼠的颈脊髓进行了基因表达微阵列分析。在受影响的代谢和信号通路中，与胆固醇相关的通路变化最为全面，包括胆固醇合成相关基因的显著下调以及胆固醇转运和代谢基因的上调。矛盾的是，观察到总胆固醇含量显著增加，这可能与胆固醇酯积累有关。为了研究胆固醇稳态失衡的潜在机制，我们对髓鞘和神经炎症相关基因及蛋白质的表达进行了定量分析。虽然髓鞘相关表达变化极小，但吞噬性小胶质细胞和星形胶质细胞增生标志物增加，尤其是在白质中。这些结果共同表明，胆固醇稳态失衡，可能是由于脊髓白质中炎症激活增加所致，可能导致衰老过程中脊髓功能受损。
