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

Wenzhen Duan; Qi Peng; Naoki Masuda; Eric Ford; Erik Tryggestad; Bruce Ladenheim; Ming Zhao; Jean Lud Cadet; John Wong; Christopher A. Ross

Neurobiology of Disease (Jun 2008)

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

Wenzhen Duan,
Qi Peng,
Naoki Masuda,
Eric Ford,
Erik Tryggestad,
Bruce Ladenheim,
Ming Zhao,
Jean Lud Cadet,
John Wong,
Christopher A. Ross

Affiliations

Wenzhen Duan: 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; Corresponding author. Fax: +1 410 614 0013.
Qi Peng: 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
Naoki Masuda: 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
Eric Ford: Department of Radiology, Johns Hopkins University School of Medicine, USA
Erik Tryggestad: Department of Radiology, Johns Hopkins University School of Medicine, USA
Bruce Ladenheim: Molecular Neuropsychiatry Branch, National Institute on Drug Abuse, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA
Ming Zhao: Oncology Analytical Pharmacology Core, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Jean Lud Cadet: Molecular Neuropsychiatry Branch, National Institute on Drug Abuse, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA
John Wong: Department of Radiology, Johns Hopkins University School of Medicine, USA
Christopher A. Ross: 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

Journal volume & issue: Vol. 30, no. 3
pp. 312 – 322

Abstract

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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.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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