The limited proliferative capacity of neuroprogenitor cells (NPCs) within the periventricular germinal niches (PGNs) located caudal of the subventricular zone (SVZ) of the lateral ventricles together with their high proliferation capacity after isolation strongly implicates cell-extrinsic humoral factors restricting NPC proliferation in the hypothalamic and midbrain PGNs. We comparatively examined the effects of norepinephrine (NE) as an endogenous candidate regulator of PGN neurogenesis in the SVZ as well as the periventricular hypothalamus and the periaqueductal midbrain. Histological and neurochemical analyses revealed that the pattern of NE innervation of the adult PGNs is inversely associated with their in vivo NPC proliferation capacity with low NE levels coupled to high NPC proliferation in the SVZ but high NE levels coupled to low NPC proliferation in hypothalamic and midbrain PGNs. Intraventricular infusion of NE decreased NPC proliferation and neurogenesis in the SVZ-olfactory bulb system, while pharmacological NE inhibition increased NPC proliferation and early neurogenesis events in the caudal PGNs. Neurotoxic ablation of NE neurons using the Dsp4-fluoxetine protocol confirmed its inhibitory effects on NPC proliferation. Contrarily, NE depletion largely impairs NPC proliferation within the hippocampus in the same animals. Our data indicate that norepinephrine has opposite effects on the two fundamental neurogenic niches of the adult brain with norepinephrine being a negative regulator of adult periventricular neurogenesis. This knowledge might ultimately lead to new therapeutic approaches to influence neurogenesis in hypothalamus-related metabolic diseases or to stimulate endogenous regenerative potential in neurodegenerative processes such as Parkinson's disease.

中文翻译：

---

去甲肾上腺素是成人脑室周围神经干细胞生态位的负调节剂。

位于侧脑室脑室下区 (SVZ) 尾部的脑室周围生发壁龛 (PGNs) 内神经祖细胞 (NPCs) 的增殖能力有限，以及分离后的高增殖能力强烈暗示细胞外源性体液因素限制了 NPC 的增殖。下丘脑和中脑 PGN。我们比较地检查了去甲肾上腺素 (NE) 作为 SVZ 以及脑室周围下丘脑和导水管周围中脑 PGN 神经发生的内源性候选调节剂的影响。组织学和神经化学分析表明，成年 PGN 的 NE 神经支配模式与其体内 NPC 增殖能力呈负相关，低 NE 水平与 SVZ 中的高 NPC 增殖相关，但高 NE 水平与下丘脑和中脑中的低 NPC 增殖相关PGN。脑室内注入 NE 降低了 SVZ 嗅球系统中的 NPC 增殖和神经发生，而药理学 NE 抑制增加了尾端 PGN 中的 NPC 增殖和早期神经发生事件。使用 Dsp4-氟西汀方案对 NE 神经元进行神经毒性消融证实了其对 NPC 增殖的抑制作用。相反，NE 耗竭在很大程度上损害了相同动物海马内 NPC 的增殖。我们的数据表明去甲肾上腺素对成人大脑的两个基本神经源性生态位具有相反的作用，去甲肾上腺素是成人脑室周围神经发生的负调节剂。这些知识可能最终导致新的治疗方法，以影响下丘脑相关代谢疾病的神经发生或刺激神经退行性疾病（如帕金森病）的内源性再生潜力。