小鼠嗅球星形胶质细胞中的多巴胺能 cAMP 信号转导

IF 4.4 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Neurochemistry international Pub Date : 2024-08-10 DOI:10.1016/j.neuint.2024.105828
Levi von Kalben , Jessica Sauer , Christine Gee , Daniela Hirnet , Christian Lohr
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引用次数: 0

摘要

环磷酸腺苷(cAMP)是几乎所有动物细胞类型(包括星形胶质细胞)中的重要第二信使。在大脑中,它调节能量代谢、发育和突触可塑性。多巴胺受体是影响腺苷酸环化酶产生 cAMP 的 G 蛋白偶联受体。多巴胺受体分为两类,一类是与Gs蛋白相连的D1类受体,可刺激cAMP的产生;另一类是与Gi/o蛋白相连的D2类受体,可抑制cAMP的产生。在本研究中,我们研究了多巴胺受体激活对小鼠嗅球星形胶质细胞中 cAMP 动态变化的影响,小鼠嗅球是多巴胺能神经元数量最多的脑区。利用基因编码的 cAMP 传感器 Flamindo2,我们对细胞膜 cAMP 浓度的变化进行了可视化分析,结果表明应用多巴胺会导致 cAMP 的短暂增加。D1 样受体激动剂 A 68930 可模拟这种 cAMP 的增加,D1 样受体拮抗剂 SCH 23390 则可抑制这种增加,而 D2 样受体配体对星形胶质细胞的 cAMP 浓度没有影响。因此,嗅球星形胶质细胞表达的D1样受体与cAMP的产生有关。
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Dopaminergic cAMP signaling in mouse olfactory bulb astrocytes

Cyclic AMP (cAMP) is an important second messenger in virtually all animal cell types, including astrocytes. In the brain, it modulates energy metabolism, development and synaptic plasticity. Dopamine receptors are G protein-coupled receptors that affect cAMP production by adenylyl cyclases. They are divided into two subgroups, D1-like receptors linked to Gs proteins stimulating cAMP production and D2-like receptors linked to Gi/o proteins inhibiting cAMP production. In the present study, we investigated the effect of dopamine receptor activation on cAMP dynamics in astrocytes of the mouse olfactory bulb, the brain region with the largest population of dopaminergic neurons. Using the genetically encoded cAMP sensor Flamindo2 we visualized changes in the cytosolic cAMP concentration and showed that dopamine application results in a transient increase in cAMP. This cAMP increase could be mimicked by the D1-like receptor agonist A 68930 and was inhibited by the D1-like receptor antagonist SCH 23390, whereas D2-like receptor ligands had no effect on the astrocytic cAMP concentration. Thus, olfactory bulb astrocytes express D1-like receptors that are linked to cAMP production.

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来源期刊
Neurochemistry international
Neurochemistry international 医学-神经科学
CiteScore
8.40
自引率
2.40%
发文量
128
审稿时长
37 days
期刊介绍: Neurochemistry International is devoted to the rapid publication of outstanding original articles and timely reviews in neurochemistry. Manuscripts on a broad range of topics will be considered, including molecular and cellular neurochemistry, neuropharmacology and genetic aspects of CNS function, neuroimmunology, metabolism as well as the neurochemistry of neurological and psychiatric disorders of the CNS.
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