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Un núcleo paraventricular excitador al circuito de neuronas AgRP que impulsa el hambre

Michael J Krashes¹, Bhavik P Shah¹, Joseph C Madara²

¹1] Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA [2] Diabetes, Endocrinology and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA (M.J.K.); National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA (M.J.K.); Cardiovascular and Metabolic Diseases, Pfizer, 610 Main Street, Cambridge, Massachusetts 02139, USA (B.P.S.); Division of Pediatric Endocrinology, Departments of Pediatrics, University of Michigan, Ann Arbor, Michigan 48105, USA (D.P.O.); Cardiovascular and Metabolic Diseases, Novartis Institutes for BioMedical Research, 100 Technology Square, Cambridge, Massachusetts 02139, USA (L.V.). [3].

|February 4, 2014

Resumen

Los investigadores descubrieron nuevas vías cerebrales que controlan el hambre. Las neuronas específicas en el hipotálamo, que expresan la hormona liberadora de tirotropina (TRH) y el polipéptido adenilato hipofisario que activa la ciclasa (PACAP), activan las neuronas del péptido relacionado con Agouti (AgRP) para impulsar el comportamiento de alimentación.

Área de la Ciencia:

La neurociencia es la neurociencia.
La neuroendocrinología en neuroendocrinología.
La regulación del apetito.

Sus antecedentes:

El hambre es un mecanismo vital de supervivencia regulado por circuitos neuronales específicos.
Las neuronas que expresan el péptido relacionado con Agouti (AgRP) en el núcleo arqueado (ARC) son reguladores clave del hambre y la alimentación.
Las fuentes de la entrada excitatoria a las neuronas AgRP, cruciales para la activación del hambre, no se habían identificado anteriormente.

Objetivo del estudio:

Para identificar las poblaciones neuronales específicas que proporcionan entrada excitatoria a las neuronas AgRP.
Investigar el papel de estos insumos recién identificados en la regulación del hambre y el comportamiento de alimentación.

Principales métodos:

Utilizó técnicas de mapeo de neuronas específicas de la célula habilitadas por la Cre-recombinasa en ratones.
Empleó la quimiogenética para estimular e inhibir poblaciones neuronales específicas.
Comportamiento de alimentación monitoreado en respuesta a la manipulación neuronal tanto en estados de saciedad como de déficit calórico.

Principales resultados:

Se identificaron nuevas entradas excitatorias en las neuronas AgRP que se originan en el núcleo paraventricular del hipotálamo.
Estas entradas surgen específicamente de subconjuntos de neuronas que expresan la hormona liberadora de tirotropina (TRH) y el polipéptido adenilato hipofisario que activa la ciclasa (PACAP).
La activación quimiogenética de estas neuronas TRH / PACAP indujo una alimentación intensa en ratones saciados, mientras que la inhibición redujo la alimentación durante la deficiencia calórica.

Conclusiones:

Se descubrió que las neuronas TRH y PACAP en el núcleo paraventricular hipotálamo proporcionan un impulso excitatorio crítico a las neuronas AgRP.
Estos hallazgos revelan una vía neuronal previamente desconocida esencial para desencadenar y regular el hambre.
Avanza en la comprensión de los complejos circuitos neuronales subyacentes al control del apetito y los estados motivacionales.

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