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Increase in excitability of hippocampal neurons during novelty-induced hyperlocomotion in dopamine-deficient mice.
Molecular Brain ( IF 3.3 ) Pub Date : 2020-09-18 , DOI: 10.1186/s13041-020-00664-8
Masayo Fujita 1 , Yukiko Ochiai 1, 2 , Taishi-Clark Takeda 1 , Yoko Hagino 1 , Kazuto Kobayashi 3 , Kazutaka Ikeda 1
Affiliation  

Dopamine is involved in many important brain functions, including voluntary motor movement. Dysfunction of the dopaminergic system can induce motor impairments, including Parkinson’s disease. We previously found that dopamine-deficient (DD) mice became hyperactive in a novel environment 72 h after the last injection of L-3,4-dihydroxyphenylalanine (L-DOPA) when dopamine was almost completely depleted. In the present study, we investigated neuronal activity in hippocampal subregions during hyperactivity by measuring Fos expression levels using immunohistochemistry. Dopamine-deficient mice were maintained on daily intraperitoneal injections of 50 mg/kg L-DOPA. Seventy-two hours after the last L-DOPA injection, DD mice were exposed to a novel environment for 1, 2, or 4 h, and then brains were collected. In wildtype mice, the number of Fos-immunopositive neurons significantly increased in the hippocampal CA1 region after 1 h of exposure to the novel environment and then decreased. In DD mice, the number of Fos-immunopositive neurons gradually increased and then significantly increased after 4 h of exposure to the novel environment. The number of Fos-immunopositive neurons also significantly increased in the CA3 region and dentate gyrus in DD mice after 4 h of exposure to the novel environment. These results indicate that the delayed and prolonged excitation of hippocampal neurons in the CA1, CA3, and dentate gyrus that is caused by dopamine depletion might be involved in hyperactivity in DD mice.

中文翻译:

在多巴胺缺陷小鼠中,新奇诱导的超运动期间海马神经元的兴奋性增加。

多巴胺参与许多重要的脑功能,包括自愿运动。多巴胺能系统功能障碍可诱发运动障碍,包括帕金森氏病。我们先前发现多巴胺缺乏症(DD)小鼠在最后一次注射L-3,4-二羟基苯丙氨酸(L-DOPA)72小时后,多巴胺几乎完全被耗尽,因此在新型环境中变得过度活跃。在本研究中,我们通过使用免疫组织化学测量Fos表达水平来研究过度活跃期间海马亚区的神经元活动。多巴胺缺乏的小鼠每天腹膜内注射50 mg / kg L-DOPA。最后一次L-DOPA注射后72小时,将DD小鼠暴露于新环境中1、2或4 h,然后收集大脑。在野生型小鼠中 暴露于新环境1 h后,海马CA1区的Fos免疫阳性神经元数量显着增加,然后下降。在DD小鼠中,暴露于新环境4 h后,Fos免疫阳性神经元的数量逐渐增加,然后显着增加。暴露于新环境4 h后,DD小鼠的CA3区和齿状回中Fos免疫阳性神经元的数量也显着增加。这些结果表明,由多巴胺耗竭引起的CA1,CA3和齿状回中海马神经元的延迟和长时间兴奋可能与DD小鼠的活动亢进有关。暴露于新环境中4 h后,Fos免疫阳性神经元的数量逐渐增加,然后显着增加。暴露于新环境4 h后,DD小鼠的CA3区和齿状回中Fos免疫阳性神经元的数量也显着增加。这些结果表明,由多巴胺耗竭引起的CA1,CA3和齿状回中海马神经元的延迟和长时间兴奋可能与DD小鼠的活动亢进有关。暴露于新环境中4 h后,Fos免疫阳性神经元的数量逐渐增加,然后显着增加。暴露于新环境4 h后,DD小鼠的CA3区和齿状回中Fos免疫阳性神经元的数量也显着增加。这些结果表明,由多巴胺耗竭引起的CA1,CA3和齿状回中海马神经元的延迟和长时间兴奋可能与DD小鼠的活动亢进有关。
更新日期:2020-09-20
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