Kv1.1 channels regulate early postnatal neurogenesis in mouse hippocampus via the TrkB signaling pathway.
Kv1.1 channels regulate early postnatal neurogenesis in mouse hippocampus via the TrkB signaling pathway.
复制标题
Kv1.1通道通过TrkB信号通路调节小鼠海马出生后早期神经发生
DOI：
10.7554/elife.58779
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发表时间：
2021-05-21
期刊：
影响因子：
7.7
通讯作者：
Yang SB
中科院分区：
文献类型：
--
作者：
Chou SM;Li KX;Huang MY;Chen C;Lin King YH;Li GG;Zhou W;Teo CF;Jan YN;Jan LY;Yang SB
在出生后的大脑中，神经发生仅发生在少数区域，如海马颗粒下区（SGZ）。出生后的神经发生受到平衡干细胞更新与分化的因素的严格调节，并且它产生参与学习和记忆形成的神经元。Kv1.1通道是一种电压门控钾通道，以前曾被证明以细胞自主的方式抑制SGZ中的出生后神经发生。在这项研究中，我们已经澄清了Kv1.1依赖的出生后神经发生的生理和分子机制。首先，我们发现神经前体细胞的膜电位在发育过程中是高度动态的。我们进一步建立了基于生物物理特征和相应细胞标志物的细胞类型分类的多项逻辑回归模型。我们发现Kv1.1通道活性的丧失导致2b型神经祖细胞的显著去极化。这种去极化与增加的原肌球蛋白受体激酶B（Trk B）信号传导和神经祖细胞增殖有关;抑制Trk B信号传导降低了出生后神经发生的程度。因此，我们的研究确定了Kv1.1钾通道在调节小鼠海马神经前体细胞增殖中的作用。
In the postnatal brain, neurogenesis occurs only within a few regions, such as the hippocampal sub-granular zone (SGZ). Postnatal neurogenesis is tightly regulated by factors that balance stem cell renewal with differentiation, and it gives rise to neurons that participate in learning and memory formation. The Kv1.1 channel, a voltage-gated potassium channel, was previously shown to suppress postnatal neurogenesis in the SGZ in a cell-autonomous manner. In this study, we have clarified the physiological and molecular mechanisms underlying Kv1.1-dependent postnatal neurogenesis. First, we discovered that the membrane potential of neural progenitor cells is highly dynamic during development. We further established a multinomial logistic regression model for cell-type classification based on the biophysical characteristics and corresponding cell markers. We found that the loss of Kv1.1 channel activity causes significant depolarization of type 2b neural progenitor cells. This depolarization is associated with increased tropomyosin receptor kinase B (TrkB) signaling and proliferation of neural progenitor cells; suppressing TrkB signaling reduces the extent of postnatal neurogenesis. Thus, our study defines the role of the Kv1.1 potassium channel in regulating the proliferation of postnatal neural progenitor cells in mouse hippocampus.
影响因子：
4.3
作者：
Yamashita M
通讯作者：
Yamashita M