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DVL-GSK3β signaling pathway

Candidate: concept label1 source documents6 linked claims
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Aliases

WNT-Dishevelled-GSK3β signaling cascade, WNT-DVL signaling cascade

Extracted Explainers

What the tool is doing

The paper presents this pathway as a regulator of susceptibility to chronic stress within the nucleus accumbens.

Source 1DOIPubMed

What problem it solves

It provides a mechanistic framework linking DVL and GSK3β regulation to depression-related behavioral phenotypes.

Source 1DOIPubMed

Evidence Snippets

These studies reveal a novel role for the DVL-GSK3β signaling pathway, acting within the brain's reward circuitry, in regulating susceptibility to chronic stress.
Evidence 1Source 1DOIPubMedprovenance

Supporting Sources

Linked Claims

Claim 1causal perturbationsupports2011Source 1DOIPubMed

Blocking DVL function in nucleus accumbens by dominant-negative DVL overexpression or pharmacological inhibition increases susceptibility to social defeat stress and promotes depression-like behavior.

Quoted textsource-backed
By using viral-mediated gene transfer to overexpress a dominant-negative mutant of DVL in NAc, or by using a pharmacological inhibitor of DVL administered into this brain region, we show that blockade of DVL function renders mice more susceptible to social defeat stress and promotes depression-like behavior in other assays.
Claim 2causal perturbationsupports2011Source 1DOIPubMed

Overexpressing GSK3β in nucleus accumbens induces prodepression-like effects, whereas overexpressing a dominant-negative mutant of GSK3β promotes resilience to social defeat stress.

Quoted textsource-backed
Similar prodepression-like effects were induced upon overexpressing GSK3β in the NAc, while overexpressing a dominant-negative mutant of GSK3β promoted resilience to social defeat stress.
Claim 3expression changesupports2011Source 1DOIPubMed

DVL2 mRNA and protein levels are downregulated in nucleus accumbens of mice susceptible to social defeat stress, but not in resilient mice.

Quoted textsource-backed
DVL2 mRNA and protein levels are downregulated in NAc of mice susceptible to social defeat stress, effects not seen in resilient mice.
Claim 4human observationsupports2011Source 1DOIPubMed

DVL is downregulated in the nucleus accumbens of depressed humans examined postmortem.

Quoted textsource-backed
Downregulation of DVL was also demonstrated in the NAc of depressed humans examined postmortem.
Claim 5mechanistic interpretationsupports2011Source 1DOIPubMed

Downregulation of DVL and phospho-GSK3β is interpreted as reflecting increased GSK3β activity.

Quoted textsource-backed
These findings are consistent with the knowledge that downregulation of DVL and phospho-GSK3β reflects an increase in GSK3β activity.
Claim 6pathway regulationsupports2011Source 1DOIPubMed

Several members of the WNT-DVL signaling cascade, including phospho-GSK3β, are downregulated in nucleus accumbens of susceptible but not resilient mice after social defeat stress.

Quoted textsource-backed
several members of the WNT (Wingless)-DVL signaling cascade, including phospho-GSK3β (glycogen synthase kinase-3β), also show significant downregulation in the NAc of susceptible, but not resilient, mice