title: Sertraline slows disease progression and increases neurogenesis in N171-82Q mouse model of Huntington's disease.
abstract: Huntington's disease (HD) is an inherited progressive neurodegenerative disorder resulting from CAG repeat expansion in the gene that encodes for the protein huntingtin. To identify neuroprotective compound (s) that can slow down disease progression and can be administered long term with few side effects in Huntington's disease, we investigated the effect of sertraline, a selective serotonin reuptake inhibitor (SSRI) which has been shown to upregulate BDNF levels in rodent brains. We report here that in HD mice sertraline increased BDNF levels, preserved chaperone protein HSP70 and Bcl-2 levels in brains, attenuated the progression of brain atrophy and behavioral abnormalities and thereby increased survival. Sertraline also enhanced neurogenesis, which appeared to be responsible for mediating the beneficial effects of sertraline in HD mice. Additionally, the effective levels of sertraline are comparable to the safe levels achievable in humans. The findings suggest that sertraline is a potential candidate for treatment of HD patients.
authors.affiliation: Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, CMSC 8-121, 600 North Wolfe Street, Baltimore, MD 21287, USA. Electronic address: wduan2@jhmi.edu.
authors.forename: Wenzhen
authors.initials: W
authors.lastname: Duan
authors.affiliation: Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, CMSC 8-121, 600 North Wolfe Street, Baltimore, MD 21287, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Peng
authors.affiliation: Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, CMSC 8-121, 600 North Wolfe Street, Baltimore, MD 21287, USA.
authors.forename: Naoki
authors.initials: N
authors.lastname: Masuda
authors.affiliation: Department of Radiology, Johns Hopkins University School of Medicine, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Ford
authors.affiliation: Department of Radiology, Johns Hopkins University School of Medicine, USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Tryggestad
authors.affiliation: Molecular Neuropsychiatry Branch, National Institute on Drug Abuse, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Ladenheim
authors.affiliation: Oncology Analytical Pharmacology Core, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Molecular Neuropsychiatry Branch, National Institute on Drug Abuse, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA.
authors.forename: Jean Lud
authors.initials: JL
authors.lastname: Cadet
authors.affiliation: Department of Radiology, Johns Hopkins University School of Medicine, USA.
authors.forename: John
authors.initials: J
authors.lastname: Wong
authors.affiliation: Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, CMSC 8-121, 600 North Wolfe Street, Baltimore, MD 21287, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Ross
mesh_terms: D000818:Animals; D001216:Asparagine / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D018450:Disease Progression; D005973:Glutamine / Q000235:genetics; D006816:Huntington Disease / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D020280:Sertraline / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D005973:Glutamine; D001216:Asparagine; D020280:Sertraline