Área de Biología Celular, Instituto de Biomedicina, Universidad de León, 24071 León, Spain.
Brain Res. 2010 Oct 28;1358:11-9. doi: 10.1016/j.brainres.2010.08.020. Epub 2010 Aug 13.
This study reports the mRNA levels of some excitatory amino acid transporters (EAATs) in response to ischemia-reperfusion (I/R) in rat hippocampus and cerebral cortex. The study was performed in 3-month-old and 18-month-old animals to analyze the possible role of age in the I/R response of these transporters. The I/R resulted in a reduced transcription of both the neuronal EAAC1 (excitatory amino acid carrier-1) and the neuronal and glial GLT-1 (glial glutamate transporter 1), while the glial GLAST1a (l-glutamate/l-aspartate transporter 1a) transcription increased following I/R. The changes observed were more striking in 3-month-old animals than in 18-month-old animals. We hypothesize that increases in the GLAST1a mRNA levels following I/R insult can be explained by increases in glial cells, while the GLT-1 response to I/R mirrors neuronal changes. GLAST1a transcription increases in 3-month-old animals support the hypothesis that this transporter would be the main mechanism for extracellular glutamate clearance after I/R. Decreases in EAAC1 and GLT-1 mRNA levels would represent either neuronal changes due to the delayed neuronal death or a putative protective down-regulation of these transporters to decrease the amount of glutamate inside the neurons, which would decrease their glutamate release. This study also reports how the treatment with the anti-inflammatory agent meloxicam attenuates the transcriptional response to I/R in 3-month-old rats and decreases the survival of the I/R-injured animals.
本研究报告了在大鼠海马体和大脑皮质中,缺血再灌注(I/R)后一些兴奋性氨基酸转运体(EAATs)的 mRNA 水平。该研究在 3 个月大和 18 个月大的动物中进行,以分析年龄在这些转运体的 I/R 反应中的可能作用。I/R 导致神经元 EAAC1(兴奋性氨基酸载体-1)和神经元和神经胶质 GLT-1(胶质谷氨酸转运体 1)的转录减少,而 GLAST1a(l-谷氨酸/l-天冬氨酸转运体 1a)的转录在 I/R 后增加。在 3 个月大的动物中观察到的变化比在 18 个月大的动物中更为明显。我们假设,I/R 损伤后 GLAST1a mRNA 水平的增加可以用胶质细胞的增加来解释,而 GLT-1 对 I/R 的反应反映了神经元的变化。3 个月大的动物中 GLAST1a 转录的增加支持了这样一种假说,即这种转运体将是 I/R 后细胞外谷氨酸清除的主要机制。EAAC1 和 GLT-1 mRNA 水平的降低要么代表由于迟发性神经元死亡引起的神经元变化,要么代表这些转运体的潜在保护性下调,以减少神经元内谷氨酸的含量,从而减少谷氨酸的释放。本研究还报告了抗炎剂美洛昔康如何减轻 3 个月大的大鼠对 I/R 的转录反应,并降低 I/R 损伤动物的存活率。