目的:颗粒下区和脑室下区的成人神经发生是公认的,但是它在其他大脑区域的存在仍然存在争议。脑室器官,例如最近被描述为成人大脑中潜在的神经源性生态位。AP是饱腹激素胰淀素的主要作用位点。胰淀素已被证明可促进新生啮齿动物中源自AP的神经元投射的形成,但胰淀素在成年神经发生中的作用尚不清楚。
方法:要对此进行测试,我们首先对急性注射胰淀素(20μg/kg)的成年大鼠的AP进行RNA测序,胰淀素加胰淀素受体拮抗剂AC187(500μg/kg)或载体。第二,动物皮下装备有释放胰淀素(50μg/kg/天)或载体的微型泵,持续3周,以使用5'-溴-2-脱氧尿苷(BrdU)技术评估细胞增殖和分化。
结果:急性胰淀素注射影响了参与控制成人神经发生的通路和过程的基因。在成年AP中,胰淀素持续上调NeuroD1转录本和蛋白质,这种效应被AC187的共同给药阻断。Further,慢性胰淀素治疗增加了新增殖的AP细胞的数量,并显著促进了它们向神经元而不是星形胶质细胞的分化.
结论:我们的发现揭示了饱腹激素胰淀素在促进成年大鼠AP神经发生中的新作用。
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.
CONCLUSIONS: Our findings revealed a novel role of the satiating hormone amylin in promoting neurogenesis in the AP of adult rats.