180 NUCLEAR FACTOR OF ACTIVATED T-CELLS (NFAT) C4 GENE DELETION CONFERS RESISTANCE TO SOCIAL STRESS INDUCED VOIDING DYSFUNCTION

Abstract

INTRODUCTION AND OBJECTIVES: Social stress induced voiding dysfunction in male mice is characterized by diminished voiding frequency and increased volume. We investigated the effect of social stress on the voiding phenotype in mice with genetic deletions of transcription factors NFAT c3 and NFAT c4. This family of transcription factors is under calcineurin control, is expressed in the forebrain, and has been shown to play a role in the consolidation of memory. We hypothesized that these mice would be resistant to the effects of social stress. METHODS: Retired c57 breeder male mice were utilized as aggressors to stress 8 week old wild type, NFAT c3, and NFAT c4 knockout mice. One hour of aggressor exposure was followed by 23 hours of barrier separation. Voiding patterns were assessed after 1 week. RESULTS: Void volume increased while number of voids decreased in stressed wild type and stressed NFAT c3 / mice compared to non-stressed control mice (p 0.05). Stressed NFAT c4 / mice had no significant change in void volume or number of voids compared to control mice (Table). Preliminary results indicate an upregulation of corticotropin releasing factor (CRF) in Barrington’s nucleus in wild type mice but not in stressed NFAT c4 / or control mice. CONCLUSIONS: Wild type and NFATc3 / mice exposed to social stress demonstrated a decline in voiding frequency and an increase in voided volumes. NFATc4 / mice, however, demonstrated voiding patterns that were identical to unstressed control mice. These results suggest that the calcineurin pathway and NFAT c4 play a key role in mediating the voiding response to social stress. CRF is upregulated in WT mice exposed to social stress compared to stressed NFAT c4 / and control mice, indicating a potential role for NFAT c4 in the forebrain in response to social stress.