Compound K induces neurogenesis of neural stem cells in thrombin induced nerve injury through LXRα signaling in mice
Compound K induces neurogenesis of neural stem cells in thrombin induced nerve injury through LXRα signaling in mice
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DOI：
10.1016/j.neulet.2020.135007
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发表时间：
2020-05
影响因子：
2.5
通讯作者：
Li Zhou;Fan Yang;Jie-wen Yin;X. Gu;Yue Xu;Yue-qin Liang
中科院分区：
文献类型：
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作者：
Li Zhou;Fan Yang;Jie-wen Yin;X. Gu;Yue Xu;Yue-qin Liang
脑出血（intracerebral hemorrhage，ICH）是由于血肿周围神经元的丢失而引起的神经功能缺损。内源性神经干细胞（EnNSC）的神经发生增加被认为增加细胞增殖和分化，从而改善神经缺陷。然而，仍然有有限的药物可有效治疗神经功能缺损。因此，我们在体内和体外建立了凝血酶诱导的小鼠模型，测定了化合物K（CK）对EnNSC的影响，并探讨了CK在促神经发生过程中的可能机制。结果显示，10 μM CK可促进凝血酶诱导的EnNSCs的神经发生、增殖，减少其凋亡。CK通过腺相关病毒基因敲除小鼠肝脏X受体α（LXRα）信号通路促进EnNSCs的神经发生。最后，腹腔注射10 mg/kg CK可改善小鼠基底节区脑室管膜下区（SVZ）的神经发生、髓鞘修复和行为缺陷，此过程涉及LXRα。这些观察结果提供了关于CK通过LXRα激活在促神经发生中的作用的证据，并建议对其进行进一步评价，因为其在ICH治疗中作为有效调节剂的潜在作用。
Intracerebral hemorrhage (ICH) causes neurological function deficit due to the loss of neurons surrounding the hematoma. Increased neurogenesis of endogenous neural stem cells (EnNSCs) is believed to increase cell proliferation and differentiation, thereby improving the neurological deficit. However, there are still limited drugs that are effective for treating neurological deficit. So, the effects of compound K (CK) in EnNSCs were measured after thrombin-induced mice models both in vivo and in vitro, and investigated the probable mechanisms of CK during pro-neurogenesis. The results revealed that 10 μM CK promotes neurogenesis, proliferation and reduces apoptosis of EnNSCs after induction by thrombin. After that, CK treatment increased the neurogenesis of EnNSCs through liver X receptor α (LXRα) signaling pathway using adeno-associated virus knockdown and knocked out mice of LXRα gene. Finally, intraperitoneal injection of 10 mg/kg CK improved the neurogenesis of subventricular zone (SVZ), myelin repair and behavioral deficit after stereotaxic injection of thrombin in the basal ganglia of mice, and this process involved LXRα. These observations provided evidence regarding the effect of CK in pro-neurogenesis via LXRα activation, and suggested further evaluation of it due to its potential role as an effective modulator in the treatment of ICH.