Dopamine regulates adult neurogenesis in the ventricular-subventricular zone via dopamine D3 angiotensin type 2 receptor interactions,STEM CELLS

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Dopamine regulates adult neurogenesis in the ventricular-subventricular zone via dopamine D3 angiotensin type 2 receptor interactions
STEM CELLS ( IF 4.0 ) Pub Date : 2021-09-14 , DOI: 10.1002/stem.3457
Maria Garcia-Garrote _{1,

2} , Juan A Parga _{1,

2} , Pablo J Labandeira ₁ , Jose Luis Labandeira-Garcia _{1,

2} , Jannette Rodriguez-Pallares _{1,

2}

Affiliation

Adult neurogenesis is a dynamic and highly regulated process, and different studies suggest that dopamine modulates ventricular-subventricular zone (V-SVZ) neurogenesis. However, the specific role of dopamine and the mechanisms/factors underlying its effects on physiological and pathological conditions such as Parkinson's disease (PD) are not fully understood. Recent studies have described counter-regulatory interactions between renin-angiotensin system (RAS) and dopamine in peripheral tissues and in the nigrostriatal system. We have previously demonstrated that angiotensin receptors regulate proliferation and generation of neuroblasts in the rodent V-SVZ. However, possible interactions between dopamine receptors and RAS in the V-SVZ and their role in alterations of neurogenesis in animal models of PD have not been investigated. In V-SVZ cultures, activation of dopamine receptors induced changes in the expression of angiotensin receptors. Moreover, dopamine, via D2-like receptors and particularly D3 receptors, increased generation of neurospheres derived from the V-SVZ and this effect was mediated by angiotensin type-2 (AT2) receptors. In rats, we observed a marked reduction in proliferation and generation of neuroblasts in the V-SVZ of dopamine-depleted animals, and inhibition of AT1 receptors or activation of AT2 receptors restored proliferation and generation of neuroblasts to control levels. Moreover, intrastriatal mesencephalic grafts partially restored proliferation and generation of neuroblasts observed in the V-SVZ of dopamine-depleted rats. Our data revealed that dopamine and angiotensin receptor interactions play a major role in the regulation of V-SVZ and suggest potential beneficial effects of RAS modulators on the regulation of adult V-SVZ neurogenesis.

中文翻译：

多巴胺通过多巴胺 D3 血管紧张素 2 型受体相互作用调节心室-心室下区的成人神经发生

成人神经发生是一个动态且高度调节的过程，不同的研究表明多巴胺调节心室-室下区 (V-SVZ) 神经发生。然而，多巴胺的具体作用及其对帕金森病 (PD) 等生理和病理状况影响的机制/因素尚不完全清楚。最近的研究描述了肾素-血管紧张素系统 (RAS) 和多巴胺在外周组织和黑质纹状体系统中的反调节相互作用。我们之前已经证明血管紧张素受体调节啮齿动物 V-SVZ 中成神经细胞的增殖和生成。然而，尚未研究 V-SVZ 中多巴胺受体和 RAS 之间可能的相互作用及其在 PD 动物模型中神经发生改变中的作用。在 V-SVZ 培养物中，多巴胺受体的激活诱导血管紧张素受体表达的变化。此外，多巴胺通过 D2 样受体，特别是 D3 受体，增加了源自 V-SVZ 的神经球的生成，这种作用是由 2 型血管紧张素 (AT2) 受体介导的。在大鼠中，我们观察到多巴胺耗尽动物的 V-SVZ 中成神经细胞的增殖和生成显着减少，并且 AT1 受体的抑制或 AT2 受体的激活使成神经细胞的增殖和生成恢复到控制水平。此外，纹状体中脑移植物部分恢复了在多巴胺耗尽大鼠的 V-SVZ 中观察到的成神经细胞的增殖和生成。

更新日期：2021-09-14

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