Abstract # 101:

Scheduled for Sunday, September 14, 2014 11:15 AM-11:30 AM: Session 15 (Henry Oliver) Oral Presentation


MODULATION OF STRESS SIGNALING PATHWAYS BY CHRONIC SOCIAL STRESS AND ANTIDEPRESSANT TREATMENT IN OLFACTORY NEUROEPITHELIAL CELLS FROM SOCIALLY-HOUSED FEMALE MACAQUES (MACACA FASCICULARIS)

S. L. Willard1, K. E. Borgmann-Winter1,2, C. A. Shively3 and C. G. Hahn1
1University of Pennsylvania, Department of Psychiatry, Philadelphia, PA 19104, USA, 2Children's Hospital of Philadelphia, 3Wake Forest School of Medicine
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     Impaired functioning of the hypothalamic-pituitary-adrenal axis, specifically glucocorticoid receptor (GR) signaling, is associated with increased stress vulnerability to neuropsychiatric disorders. Antidepressants are thought to normalize glucocorticoid dysregulation and alter nuclear translocation of GR (GRT) when administered in vitro. Since GRT is central to GR function, we hypothesized that social status and in vivo antidepressants would differentially affect GRT in neural cells of living subjects. GRT was measured in olfactory neuroepithelial cells biopsied from 24 adult female cynomolgus macaques treated for 18 months with 20 mg/kg oral sertraline or vehicle (treatment counterbalanced by social status). Cells were incubated with 1 µM dexamethasone, enriched for nuclear and cytosolic fractions, and probed for GR by Western blotting. GRT was calculated as the ratio of nuclear to cytosolic GR, and ANOVA used to determine the effects of social status and sertraline on GRT (alpha=0.05). Preliminary analysis of N=5 dominants and 11 subordinates revealed no significant interaction between social status and treatment, though the average GRT was higher in sertraline-treated compared to vehicle-treated dominants. Subordinates tended to have lower GRT than dominants, regardless of treatment (p<0.10). These preliminary results suggest that GRT may be attenuated in subordinate animals, though analysis of cells from remaining subjects is necessary. These results also demonstrate that assessments of neuronal signaling are possible in vitro instead of postmortem, thus eliminating the need to sacrifice subjects.