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在全脑缺血后 48 小时再灌注时,大鼠兴奋性氨基酸转运体(EAATs)的 mRNA 水平随年龄变化的改变。

Age-dependent modifications in the mRNA levels of the rat excitatory amino acid transporters (EAATs) at 48hour reperfusion following global ischemia.

机构信息

Área de Biología Celular, Instituto de Biomedicina, Universidad de León, 24071 León, Spain.

出版信息

Brain Res. 2010 Oct 28;1358:11-9. doi: 10.1016/j.brainres.2010.08.020. Epub 2010 Aug 13.

Abstract

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.

摘要

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。

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