Paulose C S, Chathu Finla, Khan S Reas, Krishnakumar Amee
Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin, Kerala, 682022, India.
Neurochem Res. 2008 Sep;33(9):1663-71. doi: 10.1007/s11064-007-9513-8. Epub 2007 Oct 18.
The experiments were designed to study the glutamate gene expression during epilepsy in adult and hypoxic insult to brain during the neonatal period and the therapeutic role of neuroprotective supplements. We investigated the role of metabotropic glutamate-8 receptor (mGluR8) gene expression in cerebellum during epilepsy and neuroprotective role of Bacopa monnieri extract in epilepsy. We also studied the effect of NMDA receptor 1 (NMDAR1) gene expression during neonatal hypoxia and therapeutic role of glucose, oxygen and epinephrine supplementation. During epilepsy a significant down-regulation (P < 0.01) of mGluR8 gene expression was observed which was up-regulated (P < 0.05) near control level after B. monnieri treatment which is supported by Morris water maze experiment. In hypoxic neonates we observed up-regulation (P < 0.001) of the NMDAR1 gene expression whereas glucose and glucose + oxygen was able to significantly reverse (P < 0.001) the gene expression to near control level when compared to hypoxia and epinephrine treatment which was supported by open field test. Our results showed that B. monnieri treatment to epileptic rats significantly brought the reversal of the down-regulated mgluR8 gene expression toward control level. In neonatal rats, hypoxia induced expressional and functional changes in the NMDAR1 receptors of neuronal cells which is corrected by supplementation of glucose alone or glucose followed by oxygen during the resuscitation to prevent the glutamate related neuronal damage. Thus, the results suggest the clinical significance of corrective measures for epileptic and hypoxic management.
这些实验旨在研究成年期癫痫发作期间谷氨酸基因的表达、新生儿期脑缺氧损伤情况以及神经保护补充剂的治疗作用。我们研究了代谢型谷氨酸受体8(mGluR8)基因表达在癫痫发作期间于小脑发挥的作用以及假马齿苋提取物在癫痫中的神经保护作用。我们还研究了新生儿缺氧期间N-甲基-D-天冬氨酸受体1(NMDAR1)基因表达的影响以及葡萄糖、氧气和肾上腺素补充剂的治疗作用。在癫痫发作期间,观察到mGluR8基因表达显著下调(P < 0.01),假马齿苋治疗后该基因表达上调至接近对照水平(P < 0.05),莫里斯水迷宫实验支持了这一结果。在缺氧新生儿中,我们观察到NMDAR1基因表达上调(P < 0.001),而与缺氧和肾上腺素治疗相比,葡萄糖以及葡萄糖 + 氧气能够显著将基因表达逆转至接近对照水平(P < 0.001),旷场试验支持了这一结果。我们的结果表明,对癫痫大鼠进行假马齿苋治疗可显著使下调的mgluR8基因表达逆转至对照水平。在新生大鼠中,缺氧诱导神经元细胞的NMDAR1受体发生表达和功能变化,在复苏过程中单独补充葡萄糖或先补充葡萄糖再补充氧气可纠正这种变化,以防止谷氨酸相关的神经元损伤。因此,结果表明了癫痫和缺氧治疗纠正措施的临床意义。