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 degeneration of hippocampal neurons

  • 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



Fig 1 A



Fig 1 C expression



  • DMSO expression - Dissolves ICG-001 and SP600125

  • ICG-001 – Inhibitor of Wnt signaling

  • SP600125 - Inhibitor of JNK

Fig 2A


Fig 2B expression


Fig3A expression


Fig 3B - C expression


Fig 4A expression


Fig 4 B - C expression


Fig 4D expression


Fig 5A expression


Fig 5B - C expression


Fig 6 expression


Fig 7 A - D expression


Fig 8 A-B expression


Fig 8 C expression


Discussion
Discussion expression

  • 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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