Beyond motor deficits: environmental enrichment mitigtes Huntington's disease effects in YAC128 mice

dc.contributor.authorPlácido, Evelini
dc.contributor.authorGomes Welter, Priscilla
dc.contributor.authorWink, Ana
dc.contributor.authorDuarte Karasiak, Gabriela
dc.contributor.authorFleming Outeiro, Tiago
dc.contributor.authorDafre, Alcir Luiz
dc.contributor.authorGil-Mohapel, Joana
dc.contributor.authorBrocardo, Patricia S.
dc.description.abstractHuntington’s disease (HD) is a neurodegenerative genetic disorder characterized by motor, psychiatric, cognitive, and peripheral symptoms without effective therapy. Evidence suggests that lifestyle factors can modulate disease onset and progression, and environmental enrichment (EE) has emerged as a potential approach to mitigate the progression and severity of neurodegenerative processes. Wild-type (WT) and yeast artificial chromosome (YAC) 128 mice were exposed to different EE conditions. Animals from cohort 1 were exposed to EE between postnatal days 21 and 60, and animals from cohort 2 were exposed to EE between postnatal days 60 and 120. Motor and non-motor behavioral tests were employed to evaluate the effects of EE on HD progression. Monoamine levels, hippocampal cell proliferation, neuronal differentiation, and dendritic arborization were also assessed. Here we show that EE had an antidepressant-like effect and slowed the progression of motor deficits in HD mice. It also reduced monoamine levels, which correlated with better motor performance, particularly in the striatum. EE also modulated neuronal differentiation in the YAC128 hippocampus. These results confirm that EE can impact behavior, hippocampal neuroplasticity, and monoamine levels in YAC128 mice, suggesting this could be a therapeutic strategy to modulate neuroplasticity deficits in HD. However, further research is needed to fully understand EE’s mechanisms and long-term effects as an adjuvant therapy for this debilitating condition.en_US
dc.description.sponsorshipThis work was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil. P.S.B. receives the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; Brazil) Research Productivity Fellowship-314711/2021-0. T.F.O. is supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy—EXC 2067/1-390729940. J.G.-M. acknowledges funding from the University of Victoria (UVic, Victoria, BC, Canada)–São Paulo Research Foundation (FAPESP, São Paulo, SP, Brazil) SPRINT partnership (UVic-FAPESP SPRINT 1/2018 Grant).en_US
dc.identifier.citationPlácido, E., Gomes Welter, P., Wink, A., Karasiak, G. D., Outeiro, T. F., Dafre, A. L., Gil-Mohapel, J., & Brocardo, P. S. (2023). Beyond motor deficits: Environmental enrichment mitigates Huntington’s disease effects in YAC128 mice. International Journal of Molecular Sciences, 24(16), 12607.
dc.publisherInternational Journal of Molecular Sciencesen_US
dc.subjectenvironmental enrichmenten_US
dc.subjectHuntington’s diseaseen_US
dc.subjectneuronal plasticityen_US
dc.subjecttransgenic animal modelen_US
dc.subjectYAC128 miceen_US
dc.titleBeyond motor deficits: environmental enrichment mitigtes Huntington's disease effects in YAC128 miceen_US


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