Zoloft raises BDNF, helps the HD mice

HD Lighthouse Contributing Editor's Comment: 

The Lighthouse has covered numerous studies that show that the reduction of BDNF (brain derived neurotrophic factor) is a key pathology in Huntington's Disease. One way to boost BDNF is through SSRI (selective serotonin reuptake inhibitor) antidepressants. Johns Hopkins researchers have prolonged survival time, improved symptoms, and reduced brain atrophy in the R6/2 mice through the administration of sertaline, an SSRI antidepressant with the brand name Zoloft.

A good proactive strategy for those with the gene is to try to boost BDNF levels. Exercise clearly boosts BDNF and there's some evidence that listening to music does as well.

-- Marsha L. Miller, Ph.D.
Posted to the HDL: 01-09-2008

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.

Source: Experimental Neurology 2007 Nov 9 [Epub ahead of print]