β-catenin mediates stress resilience through Dicer1microRNA regulation 20150115.pptx

Reporter: Sheng-Lan Gao(高胜兰)Advisor: Xiao-Qing Tang(唐小卿)Continued exposure to chronic stress such as pressure from work, personal issue and the loss of the beloved, some people tend to express anxiety and depression, whereas others do not. PhenomenonDespite decades of research, the molecularpathophysiology of depression remains elusive. One molecular player implicated in neuropsychiatric illnesses, including depression, is β-catenin.molecularpathophysiology β-cateninDepressionβ-catenin is a glycoprotein and it is also a multi-functional protein.upregulation of gene expressioncell-cell adhesionβ-catenincell signal transmissionnoutput of canonical Wnt signallingstructural role at synapsesThe dysfunction of β-catenin has been implicated in several neuropsychiatric disorders, including depression.β-cateninCanonical Wnt signallingCanonical Wnt signalling belongs to the so-called morp-hogen (形态发生素) pathways and plays essential roles in development and tissue homeostasis. The authors recently demonstrated the involvement of upstream Wnt signalling in the nucleus accumbens (NAc)in mouse depression models.susceptibilityWnt signallingsocial stressWnt signallingresilienceTheoretical basis Part1 Overexpressing β-catenin of normal mice with viral transgene in NAc (HSV- β-catenin)Part2 Overexpressing β-catenin of normal mice in NAc during accelerated social defeat stress (ASD)Part3 Blocking β-catenin signaling of normal mice during a sub-threshold defeat Research route Part4 Exploring the endogenous activity of β-catenin in depression(Axin2, Tcf3, Tcf4, and phospho-Ser 675 b-catenin) Transcriptional activity(Axin2, Tcf3 and Tcf4 ) in post-mortem NAc of depressed humans Axin2, Tcf3 and Tcf4 mRNA levels, and phosphoSer 675 β-catenin levels in mouse NAc after chronic social defeat stress (CSDS) Research route PART 11.1 Overexpression of β-catenin in NAc was mediated by HSV- β-catenin.NAc, nucleus accumbens HSV, herpes simplex virus单纯疱疹病毒 PART 11.2 HSV-β-catenin was in