Department of Experimental Medicine, Division of Human Physiology, Laboratory of Molecular Neurobiology, University of Palermo, Corso Tukory 129, 90134 Palermo, Italy.
Neuroscience. 2010 Feb 3;165(3):863-73. doi: 10.1016/j.neuroscience.2009.11.012. Epub 2009 Nov 10.
A number of in vitro and in vivo studies using selective agonists have indicated a neuroprotective role for group-II metabotropic glutamate (mGlu2/3) receptors in various models of neuronal injury. Although an interplay among neurotrophic factors and mGlu2/3 receptors signalling system has been suggested as possible mechanism involved on neuroprotection, at present poor information are available concerning the in vivo regulation by mGlu2/3 receptors activation of specific neurotrophic factors. By using in situ hybridization and western blotting methods the aim of present study was to analyse the potential regulatory role of selective mGluR2/3 agonist LY379268 treatment on brain derived neurotrophic factor (BDNF) expression in the mouse brain. The treatment with LY379268 evidenced a significant upregulation of BDNF mRNA levels in the cerebral cortex and in the hippocampal formation with a peak at 3 h from treatment and its disappearance already at 6 h from treatment. An analysis of dose-effect curve revealed that LY379268 may significantly enhance BDNF mRNA expression already at dose of 0.250 mg/kg b.w. The upregulation of BDNF mRNA expression was followed by a significant increase of BDNF protein levels at 24 h from LY379268 treatment. These effects of LY379268 treatment on BDNF expression were restricted to neuronal cells and were blocked by the new selective mGlu2/3 receptor antagonist LY341495, suggesting a receptor specificity. Taken together these findings suggest that several previous observed neuroprotective and trophic actions of mGluR2/3 agonists treatment may be mediated, at least in the cerebral cortex and hippocampal formation, by upregulation of BDNF expression.
许多使用选择性激动剂的体外和体内研究表明，在各种神经元损伤模型中，II 型代谢型谷氨酸（mGlu2/3）受体具有神经保护作用。尽管已经提出神经营养因子和 mGlu2/3 受体信号系统之间的相互作用可能是神经保护作用的潜在机制，但目前关于 mGlu2/3 受体激活特定神经营养因子的体内调节的信息很少。本研究采用原位杂交和 Western blot 方法，旨在分析选择性 mGluR2/3 激动剂 LY379268 处理对小鼠大脑中脑源性神经营养因子（BDNF）表达的潜在调节作用。LY379268 处理可显著上调皮质和海马结构中的 BDNF mRNA 水平，在治疗后 3 小时达到峰值，并在治疗后 6 小时消失。剂量-效应曲线分析表明，LY379268 可能在 0.250mg/kg bw 的剂量下显著增强 BDNF mRNA 的表达。LY379268 处理后 24 小时，BDNF 蛋白水平显著升高，与 BDNF mRNA 表达上调相吻合。LY379268 处理对 BDNF 表达的这些影响仅限于神经元细胞，并被新型选择性 mGlu2/3 受体拮抗剂 LY341495 阻断，表明受体具有特异性。综上所述，这些发现表明，mGluR2/3 激动剂治疗的几种先前观察到的神经保护和营养作用可能至少在大脑皮质和海马结构中，通过上调 BDNF 表达来介导。
