Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin-682 022, Kerala, India.
J Biomed Sci. 2009 Nov 10;16(1):99. doi: 10.1186/1423-0127-16-99.
Metabotrophic glutamate receptors (mGluRs) modulate cellular activities involved in the processes of differentiation and degeneration. In this study, we have analysed the expression pattern of group-I metabotropic glutamate receptor (mGlu-5) in cerebral cortex, corpus striatum, brainstem and hippocampus of streptozotocin induced and insulin treated diabetic rats (D+I) as a function of age. Also, the functional role of glutamate receptors in intra cellular calcium release from the pancreatic islets was studied in vitro. The gene expression studies showed that mGlu-5 mRNA in the cerebral cortex increased siginficantly in 7 weeks old diabetic rats whereas decreased expression was observed in brainstem, corpus striatum and hippocampus when compared to control. 90 weeks old diabetic rats showed decreased expression in cerebral cortex, corpus striatum and hippocampus whereas in brainstem the expression increased significantly compared to their respective controls. In 7 weeks old D+I group, mGlu-5 mRNA expression was significantly decreased in cerebral cortex and corpus striatum whereas the expression increased significantly in brainstem and hippocampus. 90 weeks old D+I group showed an increased expression in cerebral cortex, while it was decreased significantly in corpus striatum, brainstem and hippocampus compared to their respective controls. In vitro studies showed that glutamate at lower concentration (10(-7) M) stimulated calcium release from the pancreatic islets. Our results suggest that mGlu-5 receptors have differential expression in brain regions of diabetes and D+I groups as a function of age. This will have clinical significance in management of degeneration in brain function and memory enhancement through glutamate receptors. Also, the regulatory role of glutamate receptors in calcium release has immense therapeutic application in insulin secretion and function.
代谢型谷氨酸受体(mGluRs)调节参与分化和退化过程的细胞活动。在这项研究中,我们分析了 7 周龄和 90 周龄链脲佐菌素诱导和胰岛素治疗糖尿病大鼠(D+I)大脑皮层、纹状体、脑干和海马中 I 型代谢型谷氨酸受体(mGlu-5)的表达模式作为年龄的函数。此外,还研究了谷氨酸受体在胰腺胰岛细胞内钙释放中的功能作用。基因表达研究表明,与对照组相比,7 周龄糖尿病大鼠大脑皮层中 mGlu-5mRNA 显著增加,而脑干、纹状体和海马中表达减少。90 周龄糖尿病大鼠大脑皮层、纹状体和海马中表达减少,而脑干中表达显著增加。在 7 周龄 D+I 组中,大脑皮层和纹状体中 mGlu-5mRNA 表达显著降低,而脑干和海马中表达显著增加。90 周龄 D+I 组与各自对照组相比,大脑皮层中表达增加,而纹状体、脑干和海马中表达显著降低。体外研究表明,较低浓度(10(-7)M)的谷氨酸刺激胰腺胰岛的钙释放。我们的研究结果表明,mGlu-5 受体在糖尿病和 D+I 组的大脑区域中随年龄的不同而具有不同的表达。这将在通过谷氨酸受体管理大脑功能退化和增强记忆方面具有临床意义。此外,谷氨酸受体在钙释放中的调节作用在胰岛素分泌和功能方面具有巨大的治疗应用价值。