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双相障碍躁狂模型Clock delta19变异小鼠额叶和海马神经递质改变与行为学异常的相关性

Correlation between altered levels of neurotransmitters in the frontal lobe and hippocampus and behavioral abnormalities in a Clock delta19 mutant mice modeling bipolar manic disorder

摘要目的:探讨双相障碍躁狂模型Clock delta19变异小鼠额叶和海马神经递质改变与行为学异常的相关性。 方法:对双相障碍躁狂模型Clock delta19变异小鼠和野生型小鼠进行旷场实验和高架十字迷宫实验;分离小鼠额叶和海马,使用高效液相色谱法分析组织提取物中的神经递质;数据采用 t检验和Pearson相关分析,统计软件为SPSS22.0。 结果:(1)双相障碍躁狂模型Clock delta19变异小鼠表现出活动明显增加。(2)多巴在左侧额叶升高,在右侧海马下降;谷氨酰胺在双侧额叶下降,酪氨酸在左侧海马升高;组胺在右侧海马下降,γ-氨基丁酸(γ-aminobutyric acid,GABA)在双侧海马均下降。(3)左侧额叶谷氨酰胺和右侧海马GABA下降都和活动增加存在相关性。 结论:双相障碍躁狂模型Clock delta19变异小鼠表现出活动量增加,且左侧额叶谷氨酰胺和右侧海马GABA下降与活动增加存在相关性。

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abstractsObjective:To explore the correlation between altered levels of neurotransmitters in the frontal lobe and hippocampus and behavioral abnormalities in a Clock delta19 variant mice modeling bipolar disorder manic disorder. Methods:Open field test and Elevated plus-maze test were carried out on the Clock delta19 mutant and wild-type control groups. The frontal lobe and hippocampus of Clock delta19 mutant mice and controls were dissected, and neurotransmitters in tissue extracts were analyzed by high-performance liquid chromatography and mass spectrometry. The concentration of neurotransmitters and behavioral indicators were assessed by t test and Pearson correlation analysis using SPSS 22.0. Results:The Clock delta19 mutant mice showed a significant increase in activity, albeit with no difference in the level of anxiety from the wild-type controls, which suggested that the Clock delta19 mutant mice can be used as a model for manic attack of bipolar disorder. Altered neurotransmitter levels were detected in the frontal and hippocampal regions, including elevated histamine in the left hippocampus, reduced histamine in the right hippocampus, reduced gamma-aminobutyric acid (GABA) in bilateral hippocampus, elevated dihydroxyphenylalanine (DOPA) in the left frontal lobe and reduced DOPA in the right hippocampus, and decreased glutamine in bilateral frontal lobes. The reduced glutamine in the left frontal lobe and GABA in the right hippocampus correlated with the increased activity of Clock delta19 mutant mice. Conclusion:Clock delta19 mutant mice showed abnormal behavior with increased activity. Reduced glutamine in the left frontal lobe and GABA in the right hippocampus were correlated with increased activity.

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中华医学遗传学杂志

中华医学遗传学杂志

2020年37卷9期

991-996页

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