Brain‐derived neurotrophic factor (BDNF) signaling plays a major role in the regulation of hippocampal neurogenesis in the adult brain. While the majority of studies suggest that this is due to its effect on the survival and differentiation of newborn neurons, it remains unclear whether this signaling directly regulates neural precursor cell (NPC) activity and which of its two receptors, TrkB or the p75 neurotrophin receptor (p75^NTR) mediates this effect. Here, we examined both the RNA and protein expression of these receptors and found that TrkB but not p75^NTR receptors are expressed by hippocampal NPCs in the adult mouse brain. Using a clonal neurosphere assay, we demonstrate that pharmacological blockade of TrkB receptors directly activates a distinct subpopulation of NPCs. Moreover, we show that administration of ANA‐12, a TrkB‐selective antagonist, in vivo either by systemic intraperitoneal injection or by direct infusion within the hippocampus leads to an increase in the production of new neurons. In contrast, we found that NPC‐specific knockout of p75^NTR had no effect on the proliferation of NPCs and did not alter neurogenesis in the adult hippocampus. Collectively, these results demonstrate a novel role of TrkB receptors in directly regulating the activity of a subset of hippocampal NPCs and suggest that the transient blockade of these receptors could be used to enhance adult hippocampal neurogenesis.

中文翻译：

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TrkB的阻断而非p75NTR的阻断激活了静止神经前体细胞的亚群，并增强了成年小鼠海马的神经发生。

脑源性神经营养因子（BDNF）信号在成人脑海马神经发生的调节中起主要作用。尽管大多数研究表明这是由于其对新生神经元的存活和分化的影响，但尚不清楚该信号是否直接调节神经前体细胞（NPC）的活性以及它的两个受体TrkB或p75神经营养蛋白受体中的哪一个（p75 ^NTR）可调节此效果。在这里，我们检查了这些受体的RNA和蛋白质表达，发现TrkB而非p75 ^NTR受体由成年小鼠大脑中的海马NPC表达。使用克隆神经球测定，我们证明了TrkB受体的药理学阻断作用直接激活了NPC的独特亚群。此外，我们显示，通过全身腹膜内注射或海马内直接输注，体内施用TrkB选择性拮抗剂ANA-12会导致新神经元产生的增加。相反，我们发现NPC特异性敲除p75 ^NTR对成年海马的NPC增殖没有影响，也没有改变神经发生。总的来说，这些结果证明了TrkB受体在直接调节海马NPC子集的活性中的新作用，并暗示这些受体的瞬时阻断可用于增强成人海马神经发生。