Temporal characterization of behavioral and hippocampal dysfunction in the YAC128 mouse model of Huntington's disease

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dc.contributor.authorde Paula Nascimento-Castro, Cristine
dc.contributor.authorWinkelmann-Duarte, Elisa C.
dc.contributor.authorMancini, Gianni
dc.contributor.authorWelter, Priscilla Gomes
dc.contributor.authorPlácido, Evelini
dc.contributor.authorFarina, Marcelo
dc.contributor.authorGil-Mohapel, Joana
dc.contributor.authorRodrigues, Ana Lúcia S.
dc.contributor.authorde Bem, Andreza Fabro
dc.contributor.authorBrocardo, Patricia S.
dc.date.accessioned2022-11-12T18:25:39Z
dc.date.available2022-11-12T18:25:39Z
dc.date.copyright2022en_US
dc.date.issued2022
dc.description.abstractHuntington’s disease (HD) is a genetic neurodegenerative disease characterized by motor, psychiatric, and cognitive symptoms. Emerging evidence suggests that emotional and cognitive deficits seen in HD may be related to hippocampal dysfunction. We used the YAC128 HD mouse model to perform a temporal characterization of the behavioral and hippocampal dysfunctions. Early and late symptomatic YAC128 mice exhibited depressive-like behavior, as demonstrated by increased immobility times in the Tail Suspension Test. In addition, YAC128 mice exhibited cognitive deficits in the Swimming T-maze Test during the late symptomatic stage. Except for a reduction in basal mitochondrial respiration, no significant deficits in the mitochondrial respiratory rates were observed in the hippocampus of late symptomatic YAC128 mice. In agreement, YAC128 animals did not present robust alterations in mitochondrial ultrastructural morphology. However, light and electron microscopy analysis revealed the presence of dark neurons characterized by the intense staining of granule cell bodies and shrunken nuclei and cytoplasm in the hippocampal dentate gyrus (DG) of late symptomatic YAC128 mice. Furthermore, structural alterations in the rough endoplasmic reticulum and Golgi apparatus were detected in the hippocampal DG of YAC128 mice by electron microscopy. These results clearly show a degenerative process in the hippocampal DG in late symptomatic YAC128 animals.en_US
dc.description.reviewstatusRevieweden_US
dc.description.scholarlevelFacultyen_US
dc.description.sponsorshipP.S.B. acknowledged funding from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil) Project #480176/2013-2. ALSR, MF, AFB and PSB were recipients of CNPq Research Productivity Fellowships. J.G.M. and A.L.S.R. acknowledged funding from the Science Without Borders funding program (Programa Ciência Sem Fronteiras/CNPq), Project #403120/2012- 8) of the Brazilian Federal Government. J.G.M. also acknowledged 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.citationde Paula Nascimento-Castro, C., Winkelmann-Duarte, E., Mancini, G., Welter, P., Plácido, E., . . . Brocardo, P. (2022). “Temporal characterization of behavioral and hippocampal dysfunction in the YAC128 mouse model of Huntington’s disease.” Biomedicines, 10(6), 1433. https://doi.org/10.3390/biomedicines10061433en_US
dc.identifier.urihttps://doi.org/10.3390/biomedicines10061433
dc.identifier.urihttp://hdl.handle.net/1828/14448
dc.language.isoenen_US
dc.publisherBiomedicinesen_US
dc.subjectHuntington's disease
dc.subjecthippocampus
dc.subjectYAC128 mice
dc.subjectelectron microscopy
dc.subjectneurodegeneration
dc.subjectIsland Medical Program
dc.subject.departmentDivision of Medical Sciences
dc.subject.departmentSchool of Medical Sciences
dc.titleTemporal characterization of behavioral and hippocampal dysfunction in the YAC128 mouse model of Huntington's diseaseen_US
dc.typeArticleen_US

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