Massieu L, Tapia R
Departamento de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autonoma de México, Mexico D.F.
J Neurochem. 1997 Sep;69(3):1151-60. doi: 10.1046/j.1471-4159.1997.69031151.x.
The extracellular concentration of glutamate increases during hypoxia/ischemia probably due to deficient uptake. Glutamate might contribute to neuronal damage associated with this disorder and to neurodegeneration during aging. In the present study, we have tested the effect of two inhibitors of glutamate transport, L-trans-pyrrolidine-2,4-dicarboxylate and dihydrokainate, on the extracellular levels of glutamate and on neuronal damage, which was quantitatively studied by image analysis of histological brain sections. Drugs were administered by microdialysis and glutamate concentration was determined by HPLC in the striatum and the hippocampus of 3-month-old and 22-24-month-old rats. In both regions studied, the basal concentration of extracellular glutamate was higher in aged than in young rats. Pyrrolidine dicarboxylate induced a substantial elevation of extracellular glutamate in both regions, and although this increase was almost twofold higher in old than in young animals, no neuronal damage was observed. In contrast, dihydrokainate had a poor effect on glutamate levels, but induced clear neuronal damage in the striatum and the hippocampus in both groups of rats. The present results suggest that age appears not to be a significant factor in the sensitivity of neurons to the toxic effect of extracellular glutamate increase via blockade of its transport system.
在缺氧/缺血期间，细胞外谷氨酸浓度可能由于摄取不足而升高。谷氨酸可能导致与此疾病相关的神经元损伤以及衰老过程中的神经退行性变。在本研究中，我们测试了两种谷氨酸转运抑制剂——L-反式-吡咯烷-2,4-二羧酸和二氢卡因酸，对谷氨酸细胞外水平以及神经元损伤的影响，神经元损伤通过对组织学脑切片的图像分析进行定量研究。通过微透析给药，并用高效液相色谱法测定3月龄和22 - 24月龄大鼠纹状体和海马体中的谷氨酸浓度。在所研究的两个区域中，老年大鼠细胞外谷氨酸的基础浓度均高于年轻大鼠。吡咯烷二羧酸使两个区域的细胞外谷氨酸显著升高，尽管老年动物的这种升高几乎是年轻动物的两倍，但未观察到神经元损伤。相反，二氢卡因酸对谷氨酸水平影响不大，但在两组大鼠的纹状体和海马体中均诱导了明显的神经元损伤。目前的结果表明，年龄似乎不是神经元对通过阻断其转运系统而导致的细胞外谷氨酸增加的毒性作用敏感性的重要因素。
