The Involvement of the Decrease of Astrocytic Wnt5a in the Cognitive Decline in Minimal Hepatic Encephalopathy
The Involvement of the Decrease of Astrocytic Wnt5a in the Cognitive Decline in Minimal Hepatic Encephalopathy
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星形胶质细胞Wnt5a的减少与轻微肝性脑病认知功能下降有关
DOI：
10.1007/s12035-016-0216-5
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发表时间：
2017-12-01
影响因子：
5.1
通讯作者：
Zhuge, Qichuan
中科院分区：
文献类型：
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作者：
Ding, Saidan;Xu, Zhu;Zhuge, Qichuan
Wnt信号在神经保护和突触可塑性中起关键作用。我们推测，Wnt信号的损害可能介导星形胶质细胞神经营养因子（NTs）的生产和Wnt信号的损害星形胶质细胞NTs生产有助于轻微肝性脑病（MHE）的发病机制。在这里，我们发现星形胶质细胞NTs合成的诱导是由Wnt 5a通过PCA中的钙/钙调蛋白敏感蛋白激酶II（CaMK II）-cAMP反应元件结合蛋白（CREB）途径。Wnt 5a可逆转MHE大鼠空间学习记忆能力的下降及星形胶质细胞BDNF和NT-3的表达下调。在MHE大鼠模型中，CaMK II和CREB之间的关联增加，随后CREB响应于Wnt 5a刺激的磷酸化被抑制。我们的研究结果突出了一个新的发病机制的贡献下调NT的抑制Wnt 5a和Frizzled-2之间的相互作用在星形胶质细胞在MHE。
Wnt signaling plays a key role in neuroprotection and synaptic plasticity. We speculate that the impairment of Wnt signaling may mediate astrocytic neurotrophins (NTs) production and the impairment of Wnt signaling to astrocytic NTs production contributes to the pathogenesis of minimal hepatic encephalopathy (MHE). Here, we found that induction of astrocytic NTs synthesis was by Wnt5a via the calcium/calmodulin-sensitive protein kinase II (CaMK II)-cAMP-response element-binding protein (CREB) pathway in PCAs. The decrease of spatial learning and memory and downregulation of astrocytic BDNF and NT-3 were reversed by Wnt5a in MHE rat model. The increased association between CaMK II and CREB followed by phosphorylation of CREB in response to Wnt5a stimulation was suppressed in the MHE rat model. Our results highlight a novel pathogenesis of the contribution of downregulation of NTs to the inhibition of the interaction between Wnt5a and Frizzled-2 in astrocytes in MHE.