Gender-specific decrease in NUDR and 5-HT1A receptor proteins in the prefrontal cortex of subjects with major depressive disorder.
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.
Szewczyk
Bernadeta
B
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS 39216-4505, USA.
Albert
Paul R
PR
Burns
Ariel M
AM
Czesak
Margaret
M
Overholser
James C
JC
Jurjus
George J
GJ
Meltzer
Herbert Y
HY
Konick
Lisa C
LC
Dieter
Lesa
L
Herbst
Nicole
N
May
Warren
W
Rajkowska
Grazyna
G
Stockmeier
Craig A
CA
Austin
Mark C
MC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004268:DNA-Binding Proteins; D003865:Major Depressive Disorder / Q000473:pathology*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism*; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012727:Sex Characteristics; D014157:Transcription Factors; D055815:Young Adult
C116013:DEAF1 protein, human; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D044282:Receptor, Serotonin, 5-HT1A; D010751:Phosphopyruvate Hydratase