Roberts E L, Chih C P
Department of Neurology, University of Miami School of Medicine, FL 33136, USA.
Brain Res. 1995 Apr 24;678(1-2):83-90. doi: 10.1016/0006-8993(95)00168-p.
Aging increases the vulnerability of brain tissue to anoxia and ischemia. We investigated whether age-related alterations in energy metabolism underlie this increased vulnerability. Energy metabolism was manipulated in hippocampal slices from Fischer 344 rats of ages 6-9 (young adult), 16-19 (middle-aged adult), and 26-29 (aged adult) months by altering glucose concentrations or by using lactate instead of glucose as the metabolic substrate. Extracellular K+ activity (K+o) and synaptic excitability were monitored in stratum pyramidale of hippocampal subfield CA1. Aging diminished how well increasing concentrations of glucose delayed onset of anoxic depolarization and improved postanoxic recovery of K+o homeostasis and synaptic transmission. Hippocampal slices from all age groups responded to anoxia similarly when lactate was present instead of glucose. Also, no age-related differences were seen in normoxic ATP and phosphocreatine levels. These results suggest that an age-related decline in the glycolytic capacity of brain cells contributes to earlier onset of anoxic depolarization and poorer recovery of ion homeostasis and synaptic transmission in aging brain tissue.
衰老会增加脑组织对缺氧和缺血的易损性。我们研究了与年龄相关的能量代谢变化是否是这种易损性增加的基础。通过改变葡萄糖浓度或使用乳酸代替葡萄糖作为代谢底物，对6 - 9个月（青年成年）、16 - 19个月（中年成年）和26 - 29个月（老年成年）的Fischer 344大鼠海马切片中的能量代谢进行调控。在海马亚区CA1的锥体层监测细胞外K⁺活性（K⁺o）和突触兴奋性。衰老减弱了葡萄糖浓度增加对延迟缺氧去极化发作以及改善缺氧后K⁺o稳态和突触传递恢复的效果。当存在乳酸而非葡萄糖时，所有年龄组的海马切片对缺氧的反应相似。此外，在常氧条件下的ATP和磷酸肌酸水平未观察到与年龄相关的差异。这些结果表明，脑细胞糖酵解能力的年龄相关下降导致衰老脑组织中缺氧去极化更早发生，离子稳态和突触传递的恢复更差。
