| Autor: |
Szewczyk, Bernadeta, Albert, Paul R., Rogaeva, Anastasia, Fitzgibbon, Heidi, May, Warren L., Rajkowska, Grazyna, Miguel-Hidalgo, Jose J., Stockmeier, Craig A., Woolverton, William L., Kyle, Patrick B., Zhixia Wang, Austin, Mark C. |
| Předmět: |
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| Zdroj: |
International Journal of Neuropsychopharmacology; Sep2010, Vol. 13 Issue 8, p1089-1101, 13p |
| Abstrakt: |
Serotonin1A (5-HT1A) receptors are reported altered in the brain of subjects with major depressive disorder (MDD). Recent studies have identified transcriptional regulators of the 5-HT1A receptor and have documented gender-specific alterations in 5-HT1A transcription factor and 5-HT1A receptors in female MDD subjects. The 5k repressor element under dual repression binding protein-1 (Freud-1) is a calciumregulated repressor that negatively regulates the 5-HT1A receptor gene. This study documented the cellular expression of Freud-1 in the human prefrontal cortex (PFC) and quantified Freud-1 protein in the PFC of MDD and control subjects as well as in the PFC of rhesus monkeys chronically treated with fluoxetine. Freud-1 immunoreactivity was present in neurons and glia and was co-localized with 5-HT1A receptors. Freud-1 protein level was significantly decreased in the PFC of male MDD subjects (37%, p=0.02) relative to gender-matched control subjects. Freud-1 protein was also reduced in the PFC of female MDD subjects (36%, p=0.18) but was not statistically significant. When the data was combined across genders and analysed by age, the decrease in Freud-1 protein level was greater in the youngerMDD subjects (48%, p=0.01) relative to age-matched controls as opposed to older depressed subjects. Similarly, 5-HT1A receptor protein was significantly reduced in the PFC of the younger MDD subjects (48%, p=0.01) relative to age-matched controls. Adult male rhesus monkeys administered fluoxetine daily for 39 wk revealed no significant change in cortical Freud-1 or 5-HT1A receptor proteins compared to vehicle-treated control monkeys. Reduced protein expression of Freud-1 in MDD subjects may reflect dysregulation of this transcription factor, which may contribute to the altered regulation of 5-HT1A receptors observed in subjects with MDD. These data may also suggest that reductions in Freud-1 protein expression in the PFC may be associated with early onset of MDD. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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