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The tryptophan hydroxylase 2 (Tph2) polymorphism C2432T mediates wound repair and behavioral responses to SSRIs in a sex‐specific manner
Author(s) -
Brookshire Bethany,
Hill-Smith Tiffany E.,
Balu Darrick T,
Turner Jill,
Blendy Julie A,
Lucki Irwin
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb508
Subject(s) - tph2 , citalopram , antidepressant , serotonin , pharmacology , wound healing , tail suspension test , tryptophan hydroxylase , medicine , behavioural despair test , endocrinology , immunology , serotonergic , receptor , hippocampus
Current therapies for Major Depressive Disorder involve manipulation of brain monoamine systems, but mechanisms behind successful treatment responses remain unclear. We examined whether a novel polymorphism C2432T in the Tph2 gene mediates differences in wound repair and response to citalopram between two mouse strains, MRL/MpJ (MRL; antidepressant‐responding) compared to C57Bl/6J (C57; antidepressant‐nonresponding) (Balu et al, 2009, Clark et al, 1998). We cross‐bred the MRL and C57 strains for two generations to isolate C2432T and determine functionality using wound closure and the behavioral response to SSRIs in the tail suspension test (TST). MRL mice showed an enhanced wound healing response (p<0.001, n=10) and increased response to 20 mg/kg i.p. citalopram in the TST (p<0.001, n=10) compared to C57 mice. In the F2 generation, we observed a sex‐specific effect of C2432T on wound healing and the response to citalopram. “MRL‐like” females showed enhanced wound healing (p<0.05, n=5) and citalopram response (p<0.001, n=10), while males showed no genotype‐specific effects. The C2432T polymorphism may mediate serotonin involvement in wound repair and antidepressant response in a sex‐specific manner.