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HDAC2 regula negativamente la formación de la memoria y la plasticidad sináptica.

Ji-Song Guan¹, Stephen J Haggarty, Emanuela Giacometti

¹Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences.

|May 9, 2009

Resumen

Este resumen es generado por máquina.

La histona desacetilasa 2 (HDAC2) regula negativamente el aprendizaje y la memoria al reducir la densidad sináptica. La inhibición de HDAC2 mejora la memoria, lo que sugiere medicamentos selectivos de HDAC2 para el deterioro de la memoria.

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Área de la Ciencia:

La neurociencia es la neurociencia.
La epigenética es la epigenética.
Biología Molecular Biología Molecular

Sus antecedentes:

Las modificaciones de la cromatina, particularmente la acetilación de la histona, son cruciales para la formación de la memoria.
Los inhibidores de la histona desacetilasa (HDACis) mejoran el aprendizaje y la memoria en varios modelos.

Objetivo del estudio:

Para identificar miembros específicos de la familia de la histona desacetilasa (HDAC) involucrados en la mejora cognitiva.
Para investigar el papel de HDAC2 en la plasticidad sináptica, el aprendizaje y la memoria.

Principales métodos:

Ratones generados con sobreexpresión o deficiencia específica de la neurona de HDAC2.
Tratamiento crónico administrado con inhibidores de HDAC (HDACis).
Se evaluó la densidad de la columna dendrítica, el número de sinapsis, la plasticidad sináptica y la formación de la memoria.

Principales resultados:

La sobreexpresión neuronspecífica de HDAC2 disminuyó la densidad de la columna vertebral dendrítica, el número de sinapsis y la memoria.
La deficiencia de Hdac2 aumentó el número de sinapsis y facilitó la memoria, imitando los efectos de HDACi.
El tratamiento con HDACi mejoró los déficits de memoria en ratones con sobreexpresión de HDAC2, pero no mejoró aún más la memoria en ratones con deficiencia de Hdac2.
Se encontró que HDAC2 se asocia con promotores de genes involucrados en la plasticidad sináptica.

Conclusiones:

HDAC2 regula negativamente el aprendizaje y la memoria mediante la modulación de la plasticidad sináptica y los circuitos neuronales.
Dirigirse a HDAC2 con inhibidores selectivos puede ofrecer una estrategia terapéutica para los trastornos de deterioro de la memoria.