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1.
Int J Neuropsychopharmacol ; 13(8): 1089-101, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20392296

RESUMO

Serotonin1A (5-HT(1A)) receptors are reported altered in the brain of subjects with major depressive disorder (MDD). Recent studies have identified transcriptional regulators of the 5-HT(1A) receptor and have documented gender-specific alterations in 5-HT(1A) transcription factor and 5-HT(1A) receptors in female MDD subjects. The 5' repressor element under dual repression binding protein-1 (Freud-1) is a calcium-regulated repressor that negatively regulates the 5-HT(1A) 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-HT(1A) 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 younger MDD subjects (48%, p=0.01) relative to age-matched controls as opposed to older depressed subjects. Similarly, 5-HT(1A) 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-HT(1A) 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-HT(1A) 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.


Assuntos
Proteínas de Ligação a DNA/antagonistas & inibidores , Transtorno Depressivo Maior/metabolismo , Regulação para Baixo/fisiologia , Córtex Pré-Frontal/metabolismo , Receptor 5-HT1A de Serotonina/metabolismo , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Animais , Proteínas de Ligação a DNA/biossíntese , Transtorno Depressivo Maior/psicologia , Regulação para Baixo/genética , Feminino , Humanos , Macaca mulatta , Masculino , Pessoa de Meia-Idade , Receptor 5-HT1A de Serotonina/genética , Estudos Retrospectivos , Adulto Jovem
2.
Work ; 16(2): 77-89, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-12441461

RESUMO

This qualitative study examined the experiences of people with disabilities who use assistive technology in open employment. This study aims to describe and understand the factors the participants perceived as important in integrating technology into the workplace, as well as the barriers encountered in the process. Fifteen people with a range of acquired and congenital disabilities as well as their employers (8) or co-workers (4) were interviewed. The interviews were transcribed and analyzed. Nud*ist Version 4(R) was used for data management. Emergent themes related to the integration of assistive technology were software compatibility, Information Technology (IT) and product support, and the interaction between technology and the work environment. Participants also reported on the impact of technology on their performance and comfort at work, as well as dealing with people and processes in the workplace. By identifying the issues and support strategies for technology users in the workplace, appropriate measures can be implemented to ensure that the spirit of disability discrimination legislation is realized.

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