Downregulation of Wnt/β-catenin signaling causes degeneration of hippocampal neurons in vivo
April 1, 2011
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
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Two strains of transgenic mice: Control Axin2P-rtTA Ax2P-rtTA/TRE-Axin-EGFP
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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
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Axin∆RGS (RGS domain of Axin deleted)
Fig 1 B
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Fig 1 C
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Fig 1D
TDBTN - Total Dendritic branching tip numbers
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DMSO - Dissolves ICG-001 and SP600125
ICG-001 – Inhibitor of Wnt signaling
SP600125 - Inhibitor of JNK Fig 2A
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Fig 2B
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Fig3A
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Fig 3B - C
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Fig 4A
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Fig 4 B - C
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Fig 4D
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Fig 5A
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Fig 5B - C
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Fig 6
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Fig 7 A - D
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Fig 8 A-B
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Fig 8 C
Discussion Down-regulation of Wnt signaling causes
hippocampal neurodegeneration 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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