Temporal characterization of behavioral and hippocampal dysfunction in the YAC128 mouse model of Huntington's disease
Date
2022
Authors
de Paula Nascimento-Castro, Cristine
Winkelmann-Duarte, Elisa C.
Mancini, Gianni
Welter, Priscilla Gomes
Plácido, Evelini
Farina, Marcelo
Gil-Mohapel, Joana
Rodrigues, Ana Lúcia S.
de Bem, Andreza Fabro
Brocardo, Patricia S.
Journal Title
Journal ISSN
Volume Title
Publisher
Biomedicines
Abstract
Huntington’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.
Description
Keywords
Huntington's disease, hippocampus, YAC128 mice, electron microscopy, neurodegeneration, Island Medical Program
Citation
de 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/biomedicines10061433