Dopamine Burden Induced the Inactivation of Sonic Hedgehog Signaling to Cognitive Decline in Minimal Hepatic Encephalopathy.
Dopamine Burden Induced the Inactivation of Sonic Hedgehog Signaling to Cognitive Decline in Minimal Hepatic Encephalopathy.
复制标题
多巴胺负担导致 Sonic Hedgehog 信号失活，导致轻微肝性脑病认知能力下降
DOI：
10.14336/ad.2016.1123
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发表时间：
2017-07
影响因子：
7.4
通讯作者：
Zhuge Q
中科院分区：
文献类型：
--
作者：
Ding S;Yang J;Huang X;Liu L;Hu J;Xu Z;Zhuge Q
颅内多巴胺（DA）升高可诱发轻微肝性脑病（MHE）。然而，MHE中Shh通路与记忆丧失的关系是难以捉摸的。在本研究中，DA诱导的MHE大鼠显示Shh通路下调。此外，注射Shh到MHE/DA处理的大鼠中逆转BDNF/NT 3的下调，而给予环巴胺（Cyc）增强了对BDNF/NT 3表达的抑制。此外，柚苷（Nrg）在MHE/DA处理的大鼠中基本上预防认知障碍，并上调Shh通路，与BDNF/NT 3的表达升高平行。总之，我们的研究结果表明，Shh通路可以诱导BDNF/NT 3的表达，DA通过使MHE大鼠的Shh通路信号转导到BDNF/NT 3失活而导致记忆丧失，这被Nrg逆转。本研究为MHE的发病机制和治疗靶点提供了新的理论依据。
Minimal hepatic encephalopathy (MHE) is induced by elevated intracranial dopamine (DA). The relationship of the Shh pathway with memory loss in MHE, however, is elusive. In the current study, rats with MHE induced with DA displayed downregulation of the Shh pathway. Additionally, injection of Shh into MHE/DA-treated rats reversed downregulation of BDNF/NT3, whereas administration of cyclopamine (Cyc) enhanced the inhibition of expression of BDNF/NT3. Furthermore, naringin (Nrg) substantially prevented cognitive impairment in MHE/DA-treated rats and upregulated the Shh pathway, paralleling the elevated expression of BDNF/NT3. Overall, our results indicate that the Shh pathway can induce the expression of BDNF/NT3, and DA causes memory loss by inactivation of Shh pathway signaling to BDNF/NT3 in MHE rats, which is reversed by Nrg. Our study may provide new theory basis of pathogenesis and therapeutic target of MHE.