title: The antidepressant sertraline improves the phenotype, promotes neurogenesis and increases BDNF levels in the R6/2 Huntington's disease mouse model.
abstract: 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.
authors: Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors: Qi
authors: Q
authors: Peng
authors: Naoki
authors: N
authors: Masuda
authors: Mali
authors: M
authors: Jiang
authors: Qing
authors: Q
authors: Li
authors: Ming
authors: M
authors: Zhao
authors: Christopher A
authors: CA
authors: Ross
authors: Wenzhen
authors: W
authors: Duan
mesh_terms: D000367:Age Factors; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000097:blood; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006816:Huntington Disease / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010641:Phenotype; D020280:Sertraline / Q000008:administration & dosage* / Q000097:blood
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D009419:Nerve Tissue Proteins; D001973:Bromodeoxyuridine; D020280:Sertraline