Antidepressant Effects of Probucol on Early-Symptomatic YAC128 Transgenic Mice for Huntington’s Disease
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 als...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2018-01-01
|
| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2018/4056383 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832562798864891904 |
|---|---|
| author | Cristine de Paula Nascimento-Castro Ana Claudia Wink Victor Silva da Fônseca Claudia Daniele Bianco Elisa C. Winkelmann-Duarte Marcelo Farina Ana Lúcia S. Rodrigues Joana Gil-Mohapel Andreza Fabro de Bem Patricia S. Brocardo |
| author_facet | Cristine de Paula Nascimento-Castro Ana Claudia Wink Victor Silva da Fônseca Claudia Daniele Bianco Elisa C. Winkelmann-Duarte Marcelo Farina Ana Lúcia S. Rodrigues Joana Gil-Mohapel Andreza Fabro de Bem Patricia S. Brocardo |
| author_sort | Cristine de Paula Nascimento-Castro |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-3a66d36f1d274d5b8a89a833eda53d0d |
| institution | Kabale University |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neural Plasticity |
| spelling | doaj-art-3a66d36f1d274d5b8a89a833eda53d0d2025-02-03T01:21:48ZengWileyNeural Plasticity2090-59041687-54432018-01-01201810.1155/2018/40563834056383Antidepressant Effects of Probucol on Early-Symptomatic YAC128 Transgenic Mice for Huntington’s DiseaseCristine de Paula Nascimento-Castro0Ana Claudia Wink1Victor Silva da Fônseca2Claudia Daniele Bianco3Elisa C. Winkelmann-Duarte4Marcelo Farina5Ana Lúcia S. Rodrigues6Joana Gil-Mohapel7Andreza Fabro de Bem8Patricia S. Brocardo9Department of Morphological Sciences, Center of Biological Sciences, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC, BrazilDepartment of Morphological Sciences, Center of Biological Sciences, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC, BrazilDepartment of Morphological Sciences, Center of Biological Sciences, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC, BrazilDepartment of Morphological Sciences, Center of Biological Sciences, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC, BrazilDepartment of Morphological Sciences, Center of Biological Sciences, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC, BrazilDepartment of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC, BrazilDepartment of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC, BrazilDivision of Medical Sciences, UBC Island Medical Program, University of Victoria, Victoria, BC, V8W 2Y2, CanadaDepartment of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC, BrazilDepartment of Morphological Sciences, Center of Biological Sciences, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC, BrazilHuntington’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.http://dx.doi.org/10.1155/2018/4056383 |
| spellingShingle | Cristine de Paula Nascimento-Castro Ana Claudia Wink Victor Silva da Fônseca Claudia Daniele Bianco Elisa C. Winkelmann-Duarte Marcelo Farina Ana Lúcia S. Rodrigues Joana Gil-Mohapel Andreza Fabro de Bem Patricia S. Brocardo Antidepressant Effects of Probucol on Early-Symptomatic YAC128 Transgenic Mice for Huntington’s Disease Neural Plasticity |
| title | Antidepressant Effects of Probucol on Early-Symptomatic YAC128 Transgenic Mice for Huntington’s Disease |
| title_full | Antidepressant Effects of Probucol on Early-Symptomatic YAC128 Transgenic Mice for Huntington’s Disease |
| title_fullStr | Antidepressant Effects of Probucol on Early-Symptomatic YAC128 Transgenic Mice for Huntington’s Disease |
| title_full_unstemmed | Antidepressant Effects of Probucol on Early-Symptomatic YAC128 Transgenic Mice for Huntington’s Disease |
| title_short | Antidepressant Effects of Probucol on Early-Symptomatic YAC128 Transgenic Mice for Huntington’s Disease |
| title_sort | antidepressant effects of probucol on early symptomatic yac128 transgenic mice for huntington s disease |
| url | http://dx.doi.org/10.1155/2018/4056383 |
| work_keys_str_mv | AT cristinedepaulanascimentocastro antidepressanteffectsofprobucolonearlysymptomaticyac128transgenicmiceforhuntingtonsdisease AT anaclaudiawink antidepressanteffectsofprobucolonearlysymptomaticyac128transgenicmiceforhuntingtonsdisease AT victorsilvadafonseca antidepressanteffectsofprobucolonearlysymptomaticyac128transgenicmiceforhuntingtonsdisease AT claudiadanielebianco antidepressanteffectsofprobucolonearlysymptomaticyac128transgenicmiceforhuntingtonsdisease AT elisacwinkelmannduarte antidepressanteffectsofprobucolonearlysymptomaticyac128transgenicmiceforhuntingtonsdisease AT marcelofarina antidepressanteffectsofprobucolonearlysymptomaticyac128transgenicmiceforhuntingtonsdisease AT analuciasrodrigues antidepressanteffectsofprobucolonearlysymptomaticyac128transgenicmiceforhuntingtonsdisease AT joanagilmohapel antidepressanteffectsofprobucolonearlysymptomaticyac128transgenicmiceforhuntingtonsdisease AT andrezafabrodebem antidepressanteffectsofprobucolonearlysymptomaticyac128transgenicmiceforhuntingtonsdisease AT patriciasbrocardo antidepressanteffectsofprobucolonearlysymptomaticyac128transgenicmiceforhuntingtonsdisease |