Gender-specific decrease in NUDR and 5-HT1A receptor proteins in the prefrontal cortex of subjects with major depressive disorder

• Published in: The international journal of neuropsychopharmacology Vol. 12; no. 2; pp. 155 - 168
• Main Authors: Szewczyk, Bernadeta, Albert, Paul R., Burns, Ariel M., Czesak, Margaret, Overholser, James C., Jurjus, George J., Meltzer, Herbert Y., Konick, Lisa C., Dieter, Lesa, Herbst, Nicole, May, Warren, Rajkowska, Grazyna, Stockmeier, Craig A., Austin, Mark C.
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 01.03.2009; Oxford University Press
• Subjects: Adult; Aged; Aged, 80 and over; Case-Control Studies; Chi-Square Distribution; Depressive Disorder, Major - pathology; Female; Genotype; Humans; Male; Middle Aged; Nuclear Proteins - metabolism; Phosphopyruvate Hydratase - metabolism; Prefrontal Cortex - metabolism; Receptor, Serotonin, 5-HT1A - metabolism; Sex Characteristics; Young Adult; transcription factor; Female; 5-HT1A receptors; prefrontal cortex; major depression
• ISSN: 1461-1457; 1469-5111
• DOI: 10.1017/S1461145708009012

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.