PMID- 18096160 OWN - NLM STAT- MEDLINE DCOM- 20080502 LR - 20211020 IS - 0014-4886 (Print) IS - 1090-2430 (Electronic) IS - 0014-4886 (Linking) VI - 210 IP - 1 DP - 2008 Mar TI - The antidepressant sertraline improves the phenotype, promotes neurogenesis and increases BDNF levels in the R6/2 Huntington's disease mouse model. PG - 154-63 AB - 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. FAU - Peng, Qi AU - Peng Q AD - Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. FAU - Masuda, Naoki AU - Masuda N FAU - Jiang, Mali AU - Jiang M FAU - Li, Qing AU - Li Q FAU - Zhao, Ming AU - Zhao M FAU - Ross, Christopher A AU - Ross CA FAU - Duan, Wenzhen AU - Duan W LA - eng GR - R21 NS055942/NS/NINDS NIH HHS/United States GR - R21 NS055942-01A1/NS/NINDS NIH HHS/United States GR - NS 16375/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20071109 PL - United States TA - Exp Neurol JT - Experimental neurology JID - 0370712 RN - 0 (Antidepressive Agents) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Nerve Tissue Proteins) RN - G34N38R2N1 (Bromodeoxyuridine) RN - QUC7NX6WMB (Sertraline) SB - IM MH - Age Factors MH - Animals MH - Antidepressive Agents/*administration & dosage/blood MH - Behavior, Animal/drug effects MH - Brain/drug effects/pathology MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - Bromodeoxyuridine/metabolism MH - Cell Proliferation/*drug effects MH - Disease Models, Animal MH - Enzyme-Linked Immunosorbent Assay MH - *Huntington Disease/drug therapy/pathology/physiopathology MH - Male MH - Mice MH - Mice, Transgenic MH - Motor Activity/drug effects MH - Nerve Tissue Proteins/metabolism MH - Neurons/drug effects/*physiology MH - *Phenotype MH - Sertraline/*administration & dosage/blood PMC - PMC2278120 MID - NIHMS42162 EDAT- 2007/12/22 09:00 MHDA- 2008/05/03 09:00 PMCR- 2009/03/01 CRDT- 2007/12/22 09:00 PHST- 2007/08/15 00:00 [received] PHST- 2007/10/02 00:00 [revised] PHST- 2007/10/18 00:00 [accepted] PHST- 2007/12/22 09:00 [pubmed] PHST- 2008/05/03 09:00 [medline] PHST- 2007/12/22 09:00 [entrez] PHST- 2009/03/01 00:00 [pmc-release] AID - S0014-4886(07)00397-4 [pii] AID - 10.1016/j.expneurol.2007.10.015 [doi] PST - ppublish SO - Exp Neurol. 2008 Mar;210(1):154-63. doi: 10.1016/j.expneurol.2007.10.015. Epub 2007 Nov 9.