title: The Involvement of the Decrease of Astrocytic Wnt5a in the Cognitive Decline in Minimal Hepatic Encephalopathy.
abstract: 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.
authors.affiliation: Zhejiang Provincial Key Laboratory of Aging and Neurological Disease Research, Department of Surgery Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People's Republic of China.
authors.forename: Saidan
authors.initials: S
authors.lastname: Ding
authors.affiliation: Neurosurgery Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People's Republic of China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Neurosurgery Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People's Republic of China.
authors.forename: Jianjing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Zhejiang Provincial Key Laboratory of Aging and Neurological Disease Research, Department of Surgery Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People's Republic of China.
authors.forename: Leping
authors.initials: L
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People's Republic of China.
authors.forename: Xueli
authors.initials: X
authors.lastname: Huang
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People's Republic of China.
authors.forename: Xuebao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Neurosurgery Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People's Republic of China. firstdsdan@163.com.
authors.forename: Qichuan
authors.initials: Q
authors.lastname: Zhuge
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D060825:Cognitive Dysfunction / Q000209:etiology / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D051157:Frizzled Receptors / Q000378:metabolism*; D006501:Hepatic Encephalopathy / Q000150:complications / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D008568:Memory / Q000502:physiology; D010766:Phosphorylation; D017207:Rats, Sprague-Dawley; D000071818:Wnt-5a Protein / Q000378:metabolism*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D051157:Frizzled Receptors; D000071818:Wnt-5a Protein; C491837:Wnt5a protein, rat; C078604:Fzd2 protein, rat; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2
keywords: Astrocytes; Cognitive decline; Minimal hepatic encephalopathy; Neurotrophins; Wnt5a-Frizzled-2 signaling