A variety of studies have documented alterations in 5-HT1A receptor binding sites in the brain of subjects with major depressive disorder (MDD). The recently identified transcription factor, nuclear deformed epidermal autoregulatory factor (NUDR/Deaf-1) has been shown to function as a transcriptional modulator of the human 5-HT1A receptor gene. The present study was undertaken to document the regional and cellular localization of NUDR in the human prefrontal cortex and to examine the levels of NUDR and 5-HT1A receptor protein in prefrontal cortex of female and male depressed and control subjects. NUDR immunoreactivity was present in neurons and glia across cortical layers and was co-localized with 5-HT1A receptor immunoreactive neurons. NUDR immunoreactivity as measured by Western blot was significantly decreased in the prefrontal cortex of female depressed subjects (42%, p=0.02) and unchanged in male depressed subjects relative to gender-matched control subjects. Similarly, 5-HT1A receptor protein level was significantly reduced in the prefrontal cortex of female depressed subjects (46%, p=0.03) and unchanged in male depressed subjects compared to gender-matched control subjects. Reduced protein expression of NUDR in the prefrontal cortex of female subjects with MDD may reflect a functional alteration in this transcription factor, which may contribute to the decrease in 5-HT1A receptors observed in the same female subjects with MDD. In addition, the gender-specific alterations in cortical NUDR and 5-HT1A receptor proteins could represent an underlying biological mechanism associated with the higher incidence of depression in women.

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Background and Objective:  Simvastatin, a cholesterol‐lowering drug, also stimulates oral bone growth when applied topically, without systemic side‐effects. However, the mechanisms involved in vivo are not known. We hypothesized that bone morphogenetic protein‐2, nitric oxide synthase, and cyclooxygenase‐2 are involved, based on prior in vitro evidence. Material and Methods:  A rat bilateral mandible model, where 0.5 mg of simvastatin in methylcellulose gel was placed on one side and gel alone on the other, was used to quantify nitric oxide, cyclooxygenase‐2 and bone morphogenetic protein‐2 (via tissue extraction, enzyme activity or immunoassay), and to analyze the bone formation rate (via undecalcified histomorphometry). Cyclooxygenase‐2 and nitric oxide synthase inhibitors (NS‐398 and L‐NAME, respectively) were administered intraperitoneally. Results:  Simvastatin was found to stimulate local bone morphogenetic protein‐2, nitric oxide and the regional bone formation rate (p < 0.05), whereas NS‐398 inhibited bone morphogenetic protein‐2 and reduced the bone formation rate (p < 0.05). Conclusion:  These data suggest an association between simvastatin‐induced bone morphogenetic protein‐2 and bone formation in the mandibular microenvironment, and the negative effect of cyclooxygenase‐2 inhibitors on bone growth.