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La inducción de Slc22a3 astrocítico regula el procesamiento sensorial a través de la serotonilación de histonas
Debosmita Sardar1,2, Yi-Ting Cheng1,2,3, Junsung Woo1,2
1Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA.
Science (New York, N.Y.)
|June 15, 2023
Resumen
La actividad neuronal altera la expresión génica de los astrocitos, afectando el procesamiento sensorial. Los astrocitos regulan la liberación de serotonina y GABA, cruciales para la función olfativa.
Área de la Ciencia:
- La neurociencia
- Biología molecular
- La epigenética
Sus antecedentes:
- La actividad neuronal influye en la expresión génica en las neuronas, pero su efecto en los astrocitos vecinos sigue sin estar claro.
- Comprender las respuestas de los astrocitos es crucial para comprender la función del circuito cerebral y el procesamiento sensorial.
Objetivo del estudio:
- Investigar cómo la actividad neuronal induce cambios transcripcionales y epigenómicos en los astrocitos.
- Identificar genes específicos de los astrocitos regulados por la actividad neuronal y su papel en el procesamiento sensorial.
- Para aclarar los mecanismos por los que los astrocitos procesan la entrada neuromoduladora.
Principales métodos:
- Análisis de los cambios en la expresión génica de los astrocitos después de la actividad neuronal.
- Identificación y caracterización de los genes inducibles por la actividad de los astrocitos, incluido Slc22a3.
- Investigación del papel del Slc22a3 astrocítico en el transporte neuromodulador, los niveles de serotonina y la serotonilación histónica.
- Evaluación del impacto de la serotonilación histónica alterada en la señalización GABAérgica y la función olfativa.
Principales resultados:
- La actividad neuronal causa cambios de transcripción generalizados en los astrocitos.
- Slc22a3 fue identificado como un gen de astrocitos inducible a la actividad que regula el procesamiento sensorial en el bulbo olfativo.
- La pérdida de Slc22a3 astrocítico alteró los niveles de serotonina y la serotonilación histónica, afectando la síntesis y liberación de GABA.
- La inhibición de la serotonilación histónica en los astrocitos condujo a déficits olfativos.
Conclusiones:
- La actividad neuronal orquesta las respuestas transcripcionales y epigenómicas de los astrocitos.
- Los astrocitos procesan la entrada neuromoduladora a través de mecanismos como la serotonilación de las histonas.
- Estos mecanismos mediados por astrocitos liberan neurotransmisores, lo que influye en el procesamiento sensorial.
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