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Los distintos FGFs promueven la diferenciación de las sinapsis excitatoria e inhibidora

Akiko Terauchi¹, Erin M Johnson-Venkatesh, Anna B Toth

¹Molecular and Behavioral Neuroscience Institute, University of Michigan Medical School, Ann Arbor, Michigan 48109-2200, USA.

|May 28, 2010

Resumen

Los factores de crecimiento de los fibroblastos (FGF) organizan sinapsis cerebrales específicas. FGF22 y FGF7 guían la formación de sinapsis excitatoria e inhibidora, respectivamente, cruciales para la salud neurológica y la prevención de trastornos como la epilepsia.

Área de la Ciencia:

La neurociencia es la neurociencia.
Biología Molecular Biología Molecular
La plasticidad sináptica.

Sus antecedentes:

La función cerebral adecuada depende de las sinapsis excitatorias (glutamato) y inhibidoras (GABA) equilibradas.
Los desequilibrios están relacionados con trastornos neurológicos como el autismo, la esquizofrenia y la epilepsia.
Los mecanismos moleculares que controlan la formación de sinapsis específicas siguen siendo en gran medida desconocidos.

Objetivo del estudio:

Investigar el papel de los factores de crecimiento de los fibroblastos (FGF) en la mediación de la formación de sinapsis específicas.
Identificar los actores moleculares responsables de la organización de las terminales presinápticas excitatorias e inhibidoras.

Principales métodos:

Análisis de la expresión de FGF22 y FGF7 en las neuronas piramidal CA3 del hipocampo.
Investigando los defectos sinápticos en FGF22 y FGF7 knockout ratones.
Experimentos de rescate que involucran la expresión postsináptica de FGF.
Examinando la susceptibilidad a las convulsiones en ratones con deficiencia de FGF.

Principales resultados:

FGF22 y FGF7 actúan como organizadores derivados del objetivo para las terminales presinápticas excitatorias e inhibidoras, respectivamente.
La pérdida de FGF22 o FGF7 afecta la diferenciación específica de las sinapsis en las neuronas CA3.
La expresión postsináptica de las FGF rescata los defectos presinápticos.
La deficiencia de FGF22 confiere resistencia a la epilepsia, mientras que la deficiencia de FGF7 aumenta la susceptibilidad a las convulsiones.

Conclusiones:

Los FGF específicos (FGF22, FGF7) son organizadores presinápticos derivados de objetivos cruciales en el cerebro de los mamíferos.
Estos FGF regulan diferencialmente la formación de sinapsis excitatoria e inhibidora a través de distintas vías de localización y señalización.
La comprensión de estos mecanismos ofrece información sobre los trastornos neurológicos y posibles objetivos terapéuticos.

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