El Zoloft aumenta el FNDC, ayuda al ratón con la EH

La sertalina (Zoloft) mejora los síntomas, reduce la atrofia cerebral y prolonga la sobrevida del ratón R6/2

El Faro ha cubierto numerosos estudios que demuestran que la reducción del FNDC (factor neurotrófico derivado del cerebro) es una patología clave en la enfermedad de Huntington. Una manera de incrementar el FNDC es a través de los antidepresivos SSRI (siglas en inglés para "inhibidores selectivos del aumento de la serotonina"). Investigadores del John Hopkins prolongaron el tiempo de sobrevida, mejoraron los síntomas y redujeron la atrofia cerebral del ratón R6/2 a través des suministros de sertalina, una antidepresor SSRI con el nombre comercial Zoloft.

Una buena estrategia proactiva para quienes portan el gen, es intentar elevar sus niveles de FNDC. El ejercicio claramente aumenta el FNDC y existen algunas evidencias de que escuchar música también produce este efecto.

Marsha L. Miller, Ph.D.
Wenzhen Duan, M.D., Ph.D
The antidepressant sertraline improves the phenotype, promotes neurogenesis and increases BDNF levels in the R6/2 Huntington's disease mouse model
Qi Peng, Naoki Masuda, Mali Jiang, Qing Li, MingZhao, Christopher A. Ross and Wenzhen Duan
Huntington's disease (HD) is an inherited progressive neurodegenerative disorder characterized by progressive movement, psychiatric and cognitive disturbances. Previous studies have indicated that HD pathogenesis may be mediated in part by loss of brain derived neurotrophic factor (BDNF). Antidepressants selectively blocking serotonin reuptake can increase BDNF levels, and also may increase neurogenesis. Here we report that an SSRI antidepressant, sertraline, prolongs survival, improves motor performance, and ameliorates brain atrophy in the R6/2 HD mouse model. Six-week-old R6/2 mice and nontransgenic control mice were administered either sertraline or vehicle daily. Motor function was assessed in an accelerating rotarod test and evaluated at 10 weeks. R6/2 mice exhibited reduced time on the rod. Sertraline treatment improved the motor performance in R6/2 mice, but did not affect nontransgenic mice. R6/2 mice showed significant striatal atrophy which was reduced by sertraline treatment. These beneficial effects of sertraline are associated with enhanced neurogenesis and increased BDNF levels in brain treated with sertraline. The effective serum and brain levels of sertraline are comparable to the levels achieved in human antidepressant treatment. Our findings provide evidence that sertraline is neuroprotective in this HD model. Successful treatment with sertraline in depressed HD patients has been reported; moreover, sertraline is safe and well-tolerated for long-term administration, including in HD patients. Our findings suggest that a clinical trial of SSRI treatment in order to retard disease progression in human HD may be warranted.
Experimental Neurology 2007 Nov 9 [Epub ahead of print]