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Beyond Motor Deficits: Environmental Enrichment Mitigates Huntington’s Disease Effects in YAC128 Mice

Lookup NU author(s): Professor Tiago OuteiroORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2023 by the authors.Huntington’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.

Publication metadata

Author(s): Placido E, Gomes Welter P, Wink A, Karasiak GD, Outeiro TF, Dafre AL, Gil-Mohapel J, Brocardo PS

Publication type: Article

Publication status: Published

Journal: International Journal of Molecular Sciences

Year: 2023

Volume: 24

Issue: 16

Online publication date: 09/08/2023

Acceptance date: 07/08/2023

Date deposited: 26/09/2023

ISSN (print): 1661-6596

ISSN (electronic): 1422-0067

Publisher: Multidisciplinary Digital Publishing Institute (MDPI)


DOI: 10.3390/ijms241612607

Notes: This article belongs to the Special Issue Mechanisms and Interventions for Neurological and Psychological Disorders 2.0


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Funder referenceFunder name
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)
EXC 2067/1-390729940