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The satiating hormone amylin enhances neurogenesis in the area postrema of adult rats

機譯：飽足性激素胰島淀粉樣多肽增強成年大鼠視網(wǎng)膜后區(qū)域的神經(jīng)發(fā)生

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Objective Adult neurogenesis in the subgranular zone and subventricular zone is generally accepted, but its existence in other brain areas is still controversial. Circumventricular organs, such as the area postrema (AP) have recently been described as potential neurogenic niches in the adult brain. The AP is the major site of action of the satiating hormone amylin. Amylin has been shown to promote the formation of neuronal projections originating from the AP in neonatal rodents but the role of amylin in adult neurogenesis remains unknown. Methods To test this, we first performed an RNA-sequencing of the AP of adult rats acutely injected with either amylin (20 μg/kg), amylin plus the amylin receptor antagonist AC187 (500 μg/kg) or vehicle. Second, animals were subcutaneously equipped with minipumps releasing either amylin (50 μg/kg/day) or vehicle for 3 weeks to assess cell proliferation and differentiation with the 5′-bromo-2-deoxyuridine (BrdU) technique. Results Acute amylin injections affected genes involved in pathways and processes that control adult neurogenesis. Amylin consistently upregulated NeuroD1 transcript and protein in the adult AP, and this effect was blocked by the co-administration of AC187. Further, chronic amylin treatment increased the number of newly proliferated AP-cells and significantly promoted their differentiation into neurons rather than astrocytes. Conclusion Our findings revealed a novel role of the satiating hormone amylin in promoting neurogenesis in the AP of adult rats.
機譯：目的成人的神經(jīng)發(fā)生在顆粒下和腦室下被普遍接受，但在其他腦區(qū)的存在仍然存在爭議。近來，腦室周圍器官，例如后區(qū)域（AP），被描述為成年大腦中潛在的神經(jīng)源利基。 AP是飽足性激素胰島淀粉樣多肽的主要作用部位。胰島淀粉樣多肽已顯示出可促進新生嚙齒動物中AP產(chǎn)生的神經(jīng)元突起的形成，但胰島淀粉樣多肽在成人神經(jīng)發(fā)生中的作用仍然未知。方法為了測試這一點，我們首先對急性注射胰島淀粉樣多肽（20μg/ kg），胰島淀粉樣多肽加胰島淀粉樣多肽受體拮抗劑AC187（500μg/ kg）或媒介的成年大鼠的AP進行RNA測序。其次，為動物皮下配備微型泵，以釋放胰島淀粉樣多肽（50μg/ kg /天）或賦形劑，持續(xù)3周，以通過5'-溴-2-脫氧尿苷（BrdU）技術(shù)評估細胞增殖和分化。結(jié)果急性胰島淀粉樣蛋白注射影響涉及控制成人神經(jīng)發(fā)生的途徑和過程的基因。 Amylin持續(xù)上調(diào)成人AP中的NeuroD1轉(zhuǎn)錄和蛋白，并且這種作用被AC187的共同給藥所阻斷。此外，慢性胰島淀粉樣多肽治療增加了新增殖的AP細胞的數(shù)量，并顯著促進了它們分化為神經(jīng)元而不是星形膠質(zhì)細胞。結(jié)論我們的發(fā)現(xiàn)揭示了飽足性激素胰島淀粉樣多肽在促進成年大鼠AP神經(jīng)發(fā)生中的新作用。

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