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El miedo generalizado después del estrés agudo es causado por el cambio en la identidad del cotransmisor neuronal
Hui-Quan Li1,2, Wuji Jiang1,2, Li Ling1,2
1Neurobiology Department, School of Biological Sciences and Center for Neural Circuits and Behavior, University of California San Diego, La Jolla, CA 92093, USA.
Science (New York, N.Y.)
|March 14, 2024
Resumen
El miedo generalizado en los trastornos de ansiedad proviene de un interruptor transmisor en las neuronas del tronco cerebral. Este cambio, que involucra al glutamato y al GABA, se observó en ratones y humanos con TEPT, ofreciendo nuevos objetivos terapéuticos.
Área de la Ciencia:
- La neurociencia
- Psiquiatría molecular
- Trastornos de ansiedad
Sus antecedentes:
- La generalización del miedo a estímulos inofensivos es una característica de los trastornos de ansiedad.
- Los mecanismos neurobiológicos subyacentes de la generalización del miedo siguen siendo en gran medida desconocidos.
Objetivo del estudio:
- Para aclarar los mecanismos celulares y moleculares que impulsan la generalización del miedo.
- Identificar posibles objetivos terapéuticos para los trastornos de ansiedad caracterizados por la generalización del miedo.
Principales métodos:
- Cambios de identidad del transmisor investigados en las neuronas serotoninérgicas del núcleo dorsal del rafe en un modelo de ratón de estrés agudo.
- Se examinó el tejido cerebral postmortem de personas diagnosticadas con trastorno de estrés postraumático (TEPT).
- Evaluó el impacto de manipular el interruptor de transmisor identificado en el comportamiento de generalización del miedo.
Principales resultados:
- El miedo generalizado en ratones está mediado por un cambio de glutamato a ácido gamma-aminobutírico (GABA) en las neuronas serotoninérgicas dorsales.
- Un interruptor similar fue identificado en muestras cerebrales humanas de TEPT.
- El bloqueo de este interruptor de transmisión impidió el desarrollo del miedo generalizado.
- La activación de los receptores de corticosterona y glucocorticoides estuvo implicada en la mediación de este cambio.
- El tratamiento antidepresivo bloqueó efectivamente el interruptor transmisor y la subsiguiente generalización del miedo.
Conclusiones:
- La generalización del miedo implica un cambio neuroquímico específico en los circuitos clave del tronco cerebral.
- Este interruptor transmisor representa un mecanismo crítico en la fisiopatología de la ansiedad y el TEPT.
- Dirigirse a este interruptor ofrece una estrategia terapéutica prometedora para el tratamiento de los trastornos de ansiedad.
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