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El trastorno de estrés postraumático está asociado con PACAP y el receptor PAC1
Kerry J Ressler1, Kristina B Mercer, Bekh Bradley
1Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA. kressle@emory.edu
Nature
|February 26, 2011
Resumen
La participación de la vía del polipéptido activador de la adenilato ciclasa hipofisaria (PACAP) en el trastorno de estrés postraumático (TEPT) es específica del sexo. Los niveles más bajos de PACAP y las variantes genéticas específicas están vinculadas a los síntomas de TEPT en las mujeres, lo que sugiere un potencial biomarcador.
Área de la Ciencia:
- La neurobiología es la neurobiología.
- Genética La genética.
- La psiquiatría es la psiquiatría.
Sus antecedentes:
- El polipéptido adenilato hipofisario que activa la ciclasa (PACAP) regula ampliamente las respuestas al estrés celular.
- El papel de la vía del receptor PACAP-PAC1 en el estrés psicológico humano, específicamente el trastorno de estrés postraumático (TEPT), sigue sin estar claro.
Objetivo del estudio:
- Investigar la asociación entre la vía PACAP-PAC1 y el TEPT, centrándose en los efectos específicos del sexo.
- Identificar potenciales biomarcadores genéticos y moleculares para el TEPT dentro de la vía PACAP.
Principales métodos:
- Examinó 44 polimorfismos de nucleótido único (SNP) en los genes ADCYAP1 y ADCYAP1R1 en relación con el diagnóstico y los síntomas del TEPT.
- Se evaluaron los niveles sanguíneos de PACAP, la fisiología del miedo y la expresión del ARNm ADCYAP1R1 en sujetos humanos.
- Se utilizaron modelos de roedores para estudiar la inducción del ARNm ADCYAP1R1 bajo el condicionamiento del miedo y el reemplazo de estrógenos.
Principales resultados:
- Se encontró una asociación específica por sexo entre los niveles sanguíneos de PACAP y el TEPT en las mujeres.
- Un SNP específico (rs2267735) en ADCYAP1R1 se asoció significativamente con el diagnóstico y los síntomas de TEPT exclusivamente en mujeres.
- Este SNP se correlacionó con la discriminación del miedo y la expresión del ARNm ADCYAP1R1 en el cerebro humano, y la metilación de ADCYAP1R1 se relacionó con el TEPT.
- Los estudios en roedores mostraron la inducción del ARNm ADCYAP1R1 con el condicionamiento del miedo y el estrógeno.
Conclusiones:
- Las perturbaciones en la vía PACAP-PAC1 están implicadas en las respuestas anormales al estrés subyacentes al TEPT.
- Los efectos específicos del sexo, potencialmente mediados por la regulación del estrógeno de ADCYAP1R1, son cruciales en la fisiopatología del TEPT.
- Los niveles de PACAP y los SNPs de ADCYAP1R1 pueden servir como valiosos biomarcadores para comprender los mecanismos del TEPT.
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