Wnt2 expression and signaling is increased by different classes of antidepressant treatments.
BACKGROUND
Despite recent interest in glycogen synthase kinase-3beta (GSK-3beta) as a target for the treatment of mood disorders, there has been very little work related to these illnesses on the upstream signaling molecules that regulate this kinase as well as downstream targets.


METHODS
With a focused microarray approach we examined the influence of different classes of antidepressants on Wnt signaling that controls GSK-3beta activity as well as the transcription factors that contribute to the actions of GSK-3beta.


RESULTS
The results demonstrate that Wnt2 is a common target of different classes of antidepressants and also show differential regulation of Wnt-GSK-3beta signaling genes. Increased expression and function of Wnt2 was confirmed by secondary measures. Moreover, with a viral vector approach we demonstrate that increased expression of Wnt2 in the hippocampus is sufficient to produce antidepressant-like behavioral actions in well-established models of depression and treatment response.


CONCLUSIONS
These findings demonstrate that Wnt2 expression and signaling is a common target of antidepressants and that increased Wnt2 is sufficient to produce antidepressant effects.
Okamoto
Hideki
H
Connecticut Mental Health Center, Yale University School of Medicine, New Haven, USA.
Voleti
Bhavya
B
Banasr
Mounira
M
Sarhan
Maysa
M
Duric
Vanja
V
Girgenti
Matthew J
MJ
Dileone
Ralph J
RJ
Newton
Samuel S
SS
Duman
Ronald S
RS
D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D000229:Dependovirus / Q000235:genetics; D004597:Electroshock / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D051154:Wnt2 Protein / Q000096:biosynthesis* / Q000502:physiology
D000928:Antidepressive Agents; D051154:Wnt2 Protein