Abnormal Brain Development in Huntington' Disease Is Recapitulated in the zQ175 Knock-In Mouse Model.
Chuangchuang ZhangQian WuHongshuai LiuLiam ChengZhipeng HouSusumu MoriJun HuaChristopher A RossJiangyang ZhangPeggy C NopoulosWenzhen DuanPublished in: Cerebral cortex communications (2020)
Emerging cellular and molecular studies are providing compelling evidence that altered brain development contributes to the pathogenesis of Huntington's disease (HD). There has been lacking longitudinal system-level data obtained from in vivo HD models supporting this hypothesis. Our human MRI study in children and adolescents with HD indicates that striatal development differs between the HD and control groups, with initial hypertrophy and more rapid volume decline in HD group. In this study, we aimed to determine whether brain development recapitulates the human HD during the postnatal period. Longitudinal structural MRI scans were conducted in the heterozygous zQ175 HD mice and their littermate controls. We found that male zQ175 HD mice recapitulated the region-specific abnormal volume development in the striatum and globus pallidus, with early hypertrophy and then rapidly decline in the regional volume. In contrast, female zQ175 HD mice did not show significant difference in brain volume development with their littermate controls. This is the first longitudinal study of brain volume development at the system level in HD mice. Our results suggest that altered brain development may contribute to the HD pathogenesis. The potential effect of gene therapies targeting on neurodevelopmental event is worth to consider for HD therapeutic intervention.
Keyphrases
- mouse model
- white matter
- resting state
- randomized controlled trial
- endothelial cells
- computed tomography
- contrast enhanced
- type diabetes
- preterm infants
- machine learning
- multiple sclerosis
- early onset
- adipose tissue
- high fat diet induced
- parkinson disease
- drug delivery
- cross sectional
- electronic health record
- risk assessment
- brain injury
- subarachnoid hemorrhage
- single molecule
- artificial intelligence
- wild type
- data analysis