Antidepressant Effects of Probucol on Early-Symptomatic YAC128 Transgenic Mice for Huntington’s Disease
Joint Authors
de Paula Nascimento-Castro, Cristine
Wink, Ana Claudia
da Fônseca, Victor Silva
Bianco, Claudia Daniele
Winkelmann-Duarte, Elisa C.
Rodrigues, Ana Lúcia S.
de Bem, Andreza Fabro
Brocardo, Patricia S.
Gil-Mohapel, Joana
Farina, Marcelo
Source
Issue
Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-17, 17 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2018-08-14
Country of Publication
Egypt
No. of Pages
17
Main Subjects
Abstract EN
Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder caused by a trinucleotide expansion in the HD gene, resulting in an extended polyglutamine tract in the protein huntingtin.
HD is traditionally viewed as a movement disorder, but cognitive and neuropsychiatric symptoms also contribute to the clinical presentation.
Depression is one of the most common psychiatric disturbances in HD, present even before manifestation of motor symptoms.
Diagnosis and treatment of depression in HD-affected individuals are essential aspects of clinical management in this population, especially owing to the high risk of suicide.
This study investigated whether chronic administration of the antioxidant probucol improved motor and affective symptoms as well as hippocampal neurogenic function in the YAC128 transgenic mouse model of HD during the early- to mild-symptomatic stages of disease progression.
The motor performance and affective symptoms were monitored using well-validated behavioral tests in YAC128 mice and age-matched wild-type littermates at 2, 4, and 6 months of age, after 1, 3, or 5 months of treatment with probucol (30 mg/kg/day via water supplementation, starting on postnatal day 30).
Endogenous markers were used to assess the effect of probucol on cell proliferation (Ki-67 and proliferation cell nuclear antigen (PCNA)) and neuronal differentiation (doublecortin (DCX)) in the hippocampal dentate gyrus (DG).
Chronic treatment with probucol reduced the occurrence of depressive-like behaviors in early- and mild-symptomatic YAC128 mice.
Functional improvements were not accompanied by increased progenitor cell proliferation and neuronal differentiation.
Our findings provide evidence that administration of probucol may be of clinical benefit in the management of early- to mild-symptomatic HD.
American Psychological Association (APA)
de Paula Nascimento-Castro, Cristine& Wink, Ana Claudia& da Fônseca, Victor Silva& Bianco, Claudia Daniele& Winkelmann-Duarte, Elisa C.& Farina, Marcelo…[et al.]. 2018. Antidepressant Effects of Probucol on Early-Symptomatic YAC128 Transgenic Mice for Huntington’s Disease. Neural Plasticity،Vol. 2018, no. 2018, pp.1-17.
https://search.emarefa.net/detail/BIM-1210073
Modern Language Association (MLA)
de Paula Nascimento-Castro, Cristine…[et al.]. Antidepressant Effects of Probucol on Early-Symptomatic YAC128 Transgenic Mice for Huntington’s Disease. Neural Plasticity No. 2018 (2018), pp.1-17.
https://search.emarefa.net/detail/BIM-1210073
American Medical Association (AMA)
de Paula Nascimento-Castro, Cristine& Wink, Ana Claudia& da Fônseca, Victor Silva& Bianco, Claudia Daniele& Winkelmann-Duarte, Elisa C.& Farina, Marcelo…[et al.]. Antidepressant Effects of Probucol on Early-Symptomatic YAC128 Transgenic Mice for Huntington’s Disease. Neural Plasticity. 2018. Vol. 2018, no. 2018, pp.1-17.
https://search.emarefa.net/detail/BIM-1210073
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1210073