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La regulación de la actividad locomotora diaria y el sueño por medio de la señalización del receptor hipotalámico del
A Kramer1, F C Yang, P Snodgrass
1Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Science (New York, N.Y.)
|December 26, 2001
Resumen
El factor de crecimiento transformador-alfa (TGF-alfa), secretado por el reloj circadiano del cerebro, inhibe la actividad diaria. Esta vía involucra a los receptores del factor de crecimiento epidérmico (EGF), cruciales para regular los ciclos de sueño-vigilia y el comportamiento.
Área de la Ciencia:
- La neurociencia es la neurociencia.
- Cronobiología cronobiología.
- Biología Molecular Biología Molecular
Sus antecedentes:
- El reloj circadiano del núcleo supraquiasmático (SCN) regula los comportamientos diarios a través de factores hipotalámicos.
- El factor de crecimiento transformador-alfa (TGF-alfa) fue investigado como un potencial regulador conductual derivado de la SCN.
Objetivo del estudio:
- Para identificar los factores secretados por el SCN que influyen en la actividad locomotora.
- Para dilucidar los mecanismos neuronales subyacentes al control circadiano del comportamiento.
Principales métodos:
- Cribado sistemático para los factores inhibidos por la SCN.
- Infusión intracerebroventricular de TGF-alfa en roedores.
- Evaluación de la actividad locomotora y los patrones de sueño-vigilia.
- Utilizando ratones con mutaciones hipomórficas en el receptor del factor de crecimiento epidérmico (EGF).
Principales resultados:
- El TGF-alfa fue identificado como un inhibidor de la locomoción derivado de la SCN.
- La expresión rítmica de TGF-alfa en el SCN se correlacionó con los ritmos conductuales.
- La infusión de TGF-alfa inhibió reversiblemente la actividad y interrumpió los ciclos de sueño-vigilia.
- La señalización del receptor EGF en la zona subparaventricular medió los efectos del TGF-alfa.
- Los ratones mutantes del receptor del FEAG mostraron una actividad diurna excesiva e insensibilidad a la luz.
Conclusiones:
- La señalización de los receptores del FEAG es fundamental para el control diario de la actividad locomotora.
- Un circuito neuronal que involucra a los receptores SCN, TGF-alfa y EGF regula el comportamiento.
- Este circuito integra SCN y señales de retina para la salida de comportamiento.
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