Dopamine Protects Neurons against Glutamate-Induced Excitotoxicity

IF 1.1 Q4 CELL BIOLOGY Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Pub Date : 2023-03-29 DOI:10.1134/S1990747822060058

E. I. Fedotova, A. Y. Abramov, A. V. Berezhnov

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引用次数: 86

Abstract—

Parkinson’s disease is associated with neuronal loss in the midbrain and the resulting development of dopamine-deficient states. At the later stages of the disease, increased neuronal death is also observed in other parts of the brain. We hypothesized that dopamine may function as a glutamate antagonist, and dopamine deficiency may increase glutamate-induced excitotoxicity. Using rat hippocampal primary culture and fluorescence microscopy, we show that dopamine reduces the amplitude of calcium response evoked by the activation of NMDA receptors but does not affect calcium signals mediated by AMPA and KA receptors. Voltage-gated calcium channels are also unaffected by dopamine. It was shown that the effect of dopamine depends not only on NMDA receptors, but also on D2-type dopamine receptors and on GABA(A) receptor. Dopamine reduced glutamate-induced mitochondrial depolarization and improved neuronal survival in the presence of toxic levels of glutamate. The data presented suggest a protective role of dopamine against glutamate toxicity.

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多巴胺保护神经元免受谷氨酸诱导的兴奋性毒性

帕金森氏病与中脑神经元丢失和由此产生的多巴胺缺乏状态有关。在疾病的晚期，大脑的其他部分也观察到神经元死亡的增加。我们假设多巴胺可能作为谷氨酸拮抗剂起作用，多巴胺缺乏可能增加谷氨酸诱导的兴奋毒性。通过大鼠海马原代培养和荧光显微镜，我们发现多巴胺降低了NMDA受体激活引起的钙反应的振幅，但不影响AMPA和KA受体介导的钙信号。电压门控钙通道也不受多巴胺的影响。结果表明，多巴胺的作用不仅依赖于NMDA受体，还依赖于d2型多巴胺受体和GABA(A)受体。多巴胺减少了谷氨酸诱导的线粒体去极化，并在谷氨酸中毒水平下改善了神经元的存活。所提出的数据表明，多巴胺对谷氨酸毒性具有保护作用。

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Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology CELL BIOLOGY-

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1.40

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期刊介绍： Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology is an international peer reviewed journal that publishes original articles on physical, chemical, and molecular mechanisms that underlie basic properties of biological membranes and mediate membrane-related cellular functions. The primary topics of the journal are membrane structure, mechanisms of membrane transport, bioenergetics and photobiology, intracellular signaling as well as membrane aspects of cell biology, immunology, and medicine. The journal is multidisciplinary and gives preference to those articles that employ a variety of experimental approaches, basically in biophysics but also in biochemistry, cytology, and molecular biology. The journal publishes articles that strive for unveiling membrane and cellular functions through innovative theoretical models and computer simulations.

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