downregulation of wnt catenin signaling causes degeneration of hippocampal neurons in vivo
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Downregulation of Wnt/β-catenin signaling causes degeneration of hippocampal neurons in vivo. Introduction. Wnt binds to Frizzled or other receptors such as LRP5/6 Downstream signaling cascade including Dvl, GSK-3β, Axin

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downregulation of wnt catenin signaling causes degeneration of hippocampal neurons in vivo

Downregulation of Wnt/β-catenin signaling causes degeneration of hippocampal neurons in vivo

introduction
Introduction
  • Wnt binds to Frizzled or other receptors such as LRP5/6
    • Downstream signaling cascade including Dvl, GSK-3β, Axin
    • Accumulation of β-catenin enters nucleus and forms a complex with Tcf/Lef
    • This controls the expression of over a 100 genes
    • Autism, Alzheimer\'s disease
      • AD patients with presenilin-1 mutation have low levels of β-catenin
      • LRP6 variations (influence Tcf/Lef reporter activity) associated with late onset AD
slide4

Two strains of transgenic mice:

    • Control Axin2P-rtTA
    • Ax2P-rtTA/TRE-Axin-EGFP
slide5

Inhibition of Wnt/β-catenin via Tet-On system of Axin expression

  • DOX to forms a complex with rtTA and binds to the TRE
    • Turns on both GFP and the gene of interest (Axin)

Fig 1 A

slide9

DMSO - Dissolves ICG-001 and SP600125

  • ICG-001 – Inhibitor of Wnt signaling
  • SP600125 - Inhibitor of JNK

Fig 2A

discussion
Discussion
  • Down-regulation of Wnt signaling causes hippocampalneurodegeneration
  • Ectopically expressed β-catenin and Dvl-1 did not enhance arborization despite previous literature
    • Yu and Malenka used stabilized form of β-catenin while this study used wild type β-catenin
    • Rosso tested for Dvl-1 at 2 DIV instead of at 4 and 9 DIVC.
  • Decreased Wnt signaling may play a part in anxiety responses exhibited in patients with dementia
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