• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Neuroscience: An International Journal under the Editorial Direction of IBRO >REVERSAL OF NOVELTY-INDUCED HYPERLOCOMOTION AND HIPPOCAMPAL C-FOS EXPRESSION IN GLUA1 KNOCKOUT MALE MICE BY THE MGLUR2/3 AGONIST LY354740
【24h】

REVERSAL OF NOVELTY-INDUCED HYPERLOCOMOTION AND HIPPOCAMPAL C-FOS EXPRESSION IN GLUA1 KNOCKOUT MALE MICE BY THE MGLUR2/3 AGONIST LY354740

机译：MGLUR2 / 3激动剂LY354740逆转GLUA1基因敲除小鼠的新奇诱导的过高运动和海马C-FOS表达

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Dysfunctional glutamatergic neurotransmission has been implicated in schizophrenia and mood disorders. As a putative model for these disorders, a mouse line lacking the GluA1 subunit (GluA1-KO) of the a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) gluta-mate receptor displays a robust novelty-induced hyperloco-motion associated with excessive neuronal activation in the hippocampus. Agonists of metabotropic glutamate 2/3 receptors (mGluR2/3) inhibit glutamate release in various brain regions and they have been shown to inhibit neuronal activation in the hippocampus. Here, we tested a hypothesis that novelty-induced hyperlocomotion in the GluA1-K0 mice is mediated via excessive hippocampal neuronal activation by analyzing whether an mGluR2/3 agonist inhibits this phe-notypic feature. GluA1-K0 mice and littermate wildtype (WT) controls were administered with (1S,2S,5R,6S)-2-aminobicy-clo[3.1.0]hexane-2,6-dicarboxylic acid (LY354740) (15 mg/ kg, i.p.) 30 min before a 2-h exposure to novel arenas after which c-Fos immunopositive cells were analyzed in the hippocampus. LY354740 (15mg/kg) decreased hyperactivity in male GluA1-KO mice, with only a minimal effect in WT controls. This was observed in two cohorts of animals, one naive to handling and injections, another pre-handled and accustomed to injections. LY354740 (15mg/kg) also reduced the excessive c-Fos expression in the dorsal hippocampal CA1 pyramidal cell layer in maleGluA1-KO mice, while not affecting c-Fos levels in WT mice. In female mice, no significant effect for LY354740 (15 mg/kg) on hyperactive behavior or hippocampal c-Fos was observed in either genotype or treatment cohort. A higher dose of LY354740 (30 mg/kg) alleviated hyperlocomotion of GluA1-KO males, but not that of GluA1-KO females. In conclusion, the excessive behavioral hyperactivity of GluA1-KO mice can be partly prevented by reducing neuronal excitability in the hippocampus with the mGluR2/3 agonist suggesting that the hippocampal reactivity is strongly involved in the behavioral phenotype of GluA1-KO mice.
机译：功能异常的谷氨酸能神经传递与精神分裂症和情绪障碍有关。作为这些疾病的推定模型，缺少α-氨基-3-羟基-5-羟基-4-甲基-4-异恶唑丙酸（AMPA）谷氨酸受体的GluA1亚基（GluA1-KO）的小鼠品系显示出强大的新颖性-引起与海马神经元过度激活有关的运动过快。促代谢型谷氨酸2/3受体激动剂（mGluR2 / 3）抑制大脑各个区域的谷氨酸释放，并且已显示它们抑制海马神经元的活化。在这里，我们通过分析mGluR2 / 3激动剂是否抑制了这种phe-notypic功能，测试了一个假设，即GluA1-K0小鼠中新奇诱导的过度运动是通过过度的海马神经元激活介导的。给GluA1-K0小鼠和同窝野生型（WT）对照分别服用（1S，2S，5R，6S）-2-氨基-clo [3.1.0]己烷-2,6-二羧酸（LY354740）（15 mg / kg ，ip）在暴露于新的场所2小时之前30分钟，之后在海马中分析了c-Fos免疫阳性细胞。 LY354740（15mg / kg）降低了雄性GluA1-KO小鼠的活动过度，在WT对照中仅有极小的作用。在两个动物群中观察到了这一点，一个动物幼稚地处理和注射，另一个已经预先处理并习惯于注射。 LY354740（15mg / kg）还可减少雄性GluA1-KO小鼠背侧海马CA1锥体细胞层中过量的c-Fos表达，而不会影响WT小鼠的c-Fos水平。在雌性小鼠中，在基因型或治疗队列中均未观察到LY354740（15 mg / kg）对过度活跃行为或海马c-Fos的显着影响。较高剂量的LY354740（30 mg / kg）减轻了GluA1-KO雄性的过度运动，但没有减轻GluA1-KO雌性的过度运动。总之，可以通过使用mGluR2 / 3激动剂降低海马的神经元兴奋性来部分预防GluA1-KO小鼠过度行为亢进，这表明海马反应性强烈参与了GluA1-KO小鼠的行为表型。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号