Abnormal Brain Development in Huntington’ Disease Is Recapitulated in the zQ175 Knock-In Mouse Model

Chuangchuang Zhang; Qian Wu; Hongshuai Liu; Liam Cheng; Zhipeng Hou; Susumu Mori; Jun Hua; Christopher A Ross; Jiangyang Zhang; Peggy C Nopoulos; Wenzhen Duan

doi:10.1093/texcom/tgaa044

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Abnormal Brain Development in Huntington’ Disease Is Recapitulated in the zQ175 Knock-In Mouse Model

Journal article

Open access

Peer reviewed

Abnormal Brain Development in Huntington’ Disease Is Recapitulated in the zQ175 Knock-In Mouse Model

Chuangchuang Zhang, Qian Wu, Hongshuai Liu, Liam Cheng, Zhipeng Hou, Susumu Mori, Jun Hua, Christopher A Ross, Jiangyang Zhang, Peggy C Nopoulos, …

Cerebral Cortex Communications, Vol.1(1), pp.tgaa044-tgaa044

2020

DOI: 10.1093/texcom/tgaa044

PMCID: PMC7501464

PMID: 32984817

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https://doi.org/10.1093/texcom/tgaa044View

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Abstract

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.

Huntington’s disease

abnormal brain development

mouse model

MRI

Original

brain atrophy

Details

Title: Subtitle: Abnormal Brain Development in Huntington’ Disease Is Recapitulated in the zQ175 Knock-In Mouse Model
Creators: Chuangchuang Zhang - Division of Neurobiology
Qian Wu - Division of Neurobiology
Hongshuai Liu - Division of Neurobiology
Liam Cheng - Division of Neurobiology
Zhipeng Hou - Department of Radiology, Johns Hopkins University School of Medicine
Susumu Mori - Department of Radiology, Johns Hopkins University School of Medicine
Jun Hua - Department of Radiology, Johns Hopkins University School of Medicine
Christopher A Ross - Division of Neurobiology
Jiangyang Zhang - Deaprtment of Radiology, New York University Grossman School of Medicine
Peggy C Nopoulos - Departments of Psychiatry
Wenzhen Duan - Division of Neurobiology
Resource Type: Journal article
Publication Details: Cerebral Cortex Communications, Vol.1(1), pp.tgaa044-tgaa044
DOI: 10.1093/texcom/tgaa044
PMID: 32984817
PMCID: PMC7501464
NLM abbreviation: Cereb Cortex Commun
ISSN: 2632-7376
eISSN: 2632-7376
Publisher: Oxford University Press
Grant note: ; R21NS104480 / ; R01NS082338 / ;
Language: English
Date published: 2020
Academic Unit: Neurology; Psychiatry; Stead Family Department of Pediatrics; Iowa Neuroscience Institute
Record Identifier: 9984071995402771

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