Sertraline slows disease progression and increases neurogenesis in N171-82Q mouse model of Huntington's disease

Sertraline slows disease progression and increases neurogenesis in N171-82Q mouse model of Huntington's disease

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 si...

Full description

Bibliographic Details
Main Authors: Wenzhen Duan, Qi Peng, Naoki Masuda, Eric Ford, Erik Tryggestad, Bruce Ladenheim, Ming Zhao, Jean Lud Cadet, John Wong, Christopher A. Ross
Format: Article
Language:English
Published: Elsevier 2008-06-01
Series:Neurobiology of Disease
Subjects:
SSRI
Serotonin
BDNF
Huntington's disease
Neurogenesis
Online Access:http://www.sciencedirect.com/science/article/pii/S0969996108000259
id doaj-566e4ed1da754741b68cb88453b62b60
record_format Article
spelling doaj-566e4ed1da754741b68cb88453b62b602021-03-20T04:55:33ZengElsevierNeurobiology of Disease1095-953X2008-06-01303312322Sertraline slows disease progression and increases neurogenesis in N171-82Q mouse model of Huntington's diseaseWenzhen Duan0Qi Peng1Naoki Masuda2Eric Ford3Erik Tryggestad4Bruce Ladenheim5Ming Zhao6Jean Lud Cadet7John Wong8Christopher A. Ross9Division 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; Corresponding author. Fax: +1 410 614 0013.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, USADivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, CMSC 8-121, 600 North Wolfe Street, Baltimore, MD 21287, USADepartment of Radiology, Johns Hopkins University School of Medicine, USADepartment of Radiology, Johns Hopkins University School of Medicine, USAMolecular Neuropsychiatry Branch, National Institute on Drug Abuse, 5500 Nathan Shock Drive, Baltimore, MD 21224, USAOncology Analytical Pharmacology Core, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USAMolecular Neuropsychiatry Branch, National Institute on Drug Abuse, 5500 Nathan Shock Drive, Baltimore, MD 21224, USADepartment of Radiology, Johns Hopkins University School of Medicine, USADivision 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 21205Huntington'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.http://www.sciencedirect.com/science/article/pii/S0969996108000259SSRISerotoninBDNFHuntington's diseaseNeurogenesis
collection DOAJ
language English
format Article
sources DOAJ
author Wenzhen Duan
Qi Peng
Naoki Masuda
Eric Ford
Erik Tryggestad
Bruce Ladenheim
Ming Zhao
Jean Lud Cadet
John Wong
Christopher A. Ross
spellingShingle Wenzhen Duan
Qi Peng
Naoki Masuda
Eric Ford
Erik Tryggestad
Bruce Ladenheim
Ming Zhao
Jean Lud Cadet
John Wong
Christopher A. Ross
Sertraline slows disease progression and increases neurogenesis in N171-82Q mouse model of Huntington's disease
Neurobiology of Disease
SSRI
Serotonin
BDNF
Huntington's disease
Neurogenesis
author_facet Wenzhen Duan
Qi Peng
Naoki Masuda
Eric Ford
Erik Tryggestad
Bruce Ladenheim
Ming Zhao
Jean Lud Cadet
John Wong
Christopher A. Ross
author_sort Wenzhen Duan
title Sertraline slows disease progression and increases neurogenesis in N171-82Q mouse model of Huntington's disease
title_short Sertraline slows disease progression and increases neurogenesis in N171-82Q mouse model of Huntington's disease
title_full Sertraline slows disease progression and increases neurogenesis in N171-82Q mouse model of Huntington's disease
title_fullStr Sertraline slows disease progression and increases neurogenesis in N171-82Q mouse model of Huntington's disease
title_full_unstemmed Sertraline slows disease progression and increases neurogenesis in N171-82Q mouse model of Huntington's disease
title_sort sertraline slows disease progression and increases neurogenesis in n171-82q mouse model of huntington's disease
publisher Elsevier
series Neurobiology of Disease
issn 1095-953X
publishDate 2008-06-01
description 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.
topic SSRI
Serotonin
BDNF
Huntington's disease
Neurogenesis
url http://www.sciencedirect.com/science/article/pii/S0969996108000259
work_keys_str_mv AT wenzhenduan sertralineslowsdiseaseprogressionandincreasesneurogenesisinn17182qmousemodelofhuntingtonsdisease
AT qipeng sertralineslowsdiseaseprogressionandincreasesneurogenesisinn17182qmousemodelofhuntingtonsdisease
AT naokimasuda sertralineslowsdiseaseprogressionandincreasesneurogenesisinn17182qmousemodelofhuntingtonsdisease
AT ericford sertralineslowsdiseaseprogressionandincreasesneurogenesisinn17182qmousemodelofhuntingtonsdisease
AT eriktryggestad sertralineslowsdiseaseprogressionandincreasesneurogenesisinn17182qmousemodelofhuntingtonsdisease
AT bruceladenheim sertralineslowsdiseaseprogressionandincreasesneurogenesisinn17182qmousemodelofhuntingtonsdisease
AT mingzhao sertralineslowsdiseaseprogressionandincreasesneurogenesisinn17182qmousemodelofhuntingtonsdisease
AT jeanludcadet sertralineslowsdiseaseprogressionandincreasesneurogenesisinn17182qmousemodelofhuntingtonsdisease
AT johnwong sertralineslowsdiseaseprogressionandincreasesneurogenesisinn17182qmousemodelofhuntingtonsdisease
AT christopheraross sertralineslowsdiseaseprogressionandincreasesneurogenesisinn17182qmousemodelofhuntingtonsdisease
_version_ 1724211707532804096

Similar Items