Evidence revealing deregulation of the KLF11-MAO A pathway in association with chronic stress and depressive disorders.
Neuropsychopharmacology
; 40(6): 1373-82, 2015 May.
Article
en En
| MEDLINE
| ID: mdl-25502632
ABSTRACT
The biochemical pathways underlying major depressive disorder (MDD) and chronic stress are not well understood. However, it has been reported that monoamine oxidase A (MAO A, a major neurotransmitter-degrading enzyme) is significantly increased in the brains of human subjects affected with MDD and rats exposed to chronic social defeat (CSD) stress, which is used to model depression. In the current study, we compared the protein levels of a MAO A-transcriptional activator, Kruppel-like factor 11 (KLF11 , also recognized as transforming growth factor-beta-inducible early gene 2) between the brains of 18 human subjects with MDD and 18 control subjects. We found that, indeed, the expression of KLF11 is increased by 36% (p<0.02) in the postmortem prefrontal cortex of human subjects with MDD compared with controls. We also observed a positive correlation between KLF11 levels and those of its target gene, MAO A, both in association with MDD. KLF11 protein expression was also increased by 44% (p<0.02) in the frontal cortex of KLF11 wild-type mice (Klf11(+/+)) vs Klf11(-/-) when both exposed to CSD stress. In contrast, locomotor activities, central box duration and sucrose preference were significantly reduced in the stressed Klf11(+/+) mice, suggesting that Klf11(+/+) mice are more severely affected by the stress model compared with Klf11(-/-) mice. These results serve to assign an important role of KLF11 in upregulating MAO A in MDD and chronic social stress, suggesting that inhibition of the pathways regulated by this transcription factor may aid in the therapeutics of neuropsychiatric illnesses. Thus, the new knowledge derived from the current study extends our understanding of transcriptional mechanisms that are operational in the pathophysiology of common human diseases and thus bears significant biomedical relevance.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
6_mental_health_behavioral_disorders
Asunto principal:
Proteínas Represoras
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Estrés Psicológico
/
Factores de Transcripción
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Proteínas de Ciclo Celular
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Trastorno Depresivo Mayor
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Proteínas de Unión al ADN
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Lóbulo Frontal
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Monoaminooxidasa
Tipo de estudio:
Prognostic_studies
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Risk_factors_studies
Límite:
Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Neuropsychopharmacology
Asunto de la revista:
NEUROLOGIA
/
PSICOFARMACOLOGIA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos