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Cited by 23Schizophrenia research and treatmentNeurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology Research

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Brain volumetric alterations accompanied with loss of striatal medium-sized spiny neurons and cortical parvalbumin expressing interneurons in Brd1+/− mice

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Qvist, Per, Eskildsen, Simon F., Hansen, Brian, Baragji, Mohammad, Ringgaard, Steffen, Roovers, Jolien, Paternoster, Veerle, Molgaard, Simon, Corydon, Thomas Juhl, Stødkilde-Jørgensen, Hans, Glerup, Simon, Mors, Ole, Wegener, Gregers, Nyengaard, Jens R., Børglum, Anders D., Christensen, Jane H.·2018·Scientific Reports
DOI 10.1038/s41598-018-34729-5PMC PMC6220279
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Abstract

Schizophrenia is a common and severe mental disorder arising from complex gene-environment interactions affecting brain development and functioning. While a consensus on the neuroanatomical correlates of schizophrenia is emerging, much of its fundamental pathobiology remains unknown. In this study, we explore brain morphometry in mice with genetic susceptibility and phenotypic relevance to schizophrenia (Brd1+/− mice) using postmortem 3D MR imaging coupled with histology, immunostaining and regional mRNA marker analysis. In agreement with recent large-scale schizophrenia neuroimaging studies, Brd1+/− mice displayed subcortical abnormalities, including volumetric reductions of amygdala and striatum. Interestingly, we demonstrate that structural alteration in striatum correlates with a general loss of striatal neurons, differentially impacting subpopulations of medium-sized spiny neurons and thus potentially striatal output. Akin to parvalbumin interneuron dysfunction in patients, a decline in parvalbumin expression was noted in the developing cortex of Brd1+/− mice, mainly driven by neuronal loss within or near cortical layer V, which is rich in corticostriatal projection neurons. Collectively, our study highlights the translational value of the Brd1+/− mouse as a pre-clinical tool for schizophrenia research and provides novel insight into its developmental, structural, and cellular pathology.

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  • Volumetric analysis shows that caudate-putamen averages 20.5 ± 0.5μL in mice, with the extracellular space composing 3.1 μL.

    “Volumetric analysis shows that caudate–putamen averages 20.5 ± 0.5μL in mice15, with the extracellular space composing 3.1 μL.”

    From A curious concept of CNS clearance (2025) · cites this paper as [15]

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Metadata

Authors
Qvist, P., Eskildsen, S. F., Hansen, B., Baragji, M., Ringgaard, S., Roovers, J., Paternoster, V., Molgaard, S., Corydon, T. J., Stødkilde-Jørgensen, H., Glerup, S., Mors, O., Wegener, G., Nyengaard, J. R., Børglum, A. D., & Christensen, J. H.
Affiliations
  • Aarhus University (DK)
  • Aarhus University Hospital (DK)
Corresponding author
  • Qvist, Per
  • Corydon, Thomas Juhl
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2018-11-07
Volume
8
Issue
1
Pages
16486-16486
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-018-34729-5
PMC
PMC6220279
OpenAlex
W2899288958
Cited by
23
References
4
Citations by year
2026: 3 · 2025: 3 · 2024: 3 · 2022: 4 · 2021: 7 · 2020: 2 · 2018: 1
FWCI
1.80
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Scopus (Elsevier) (submittedVersion)
Funders
  • Aarhus Universitet
  • Villum Fonden
  • Lundbeckfonden (R198-2015-168, R248‐2017‐2003)
  • Novo Nordisk
  • Danmarks Frie Forskningsfond
  • Augustinus Fonden
  • Riisfort Fonden
  • Novo Nordisk Fonden
  • H. Lundbeck A/S
  • Sundhedsvidenskabelige Fakultet, Aarhus Universitet
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
schizophrenia, brain morphometry, striatum, amygdala, parvalbumin interneurons, cortical layer V, striatal output, neuronal loss, 3D MRI, mouse model
MeSH terms
Bromodomain Containing Proteins, Animals, Brain, Cell Count, Corpus Striatum, Heterozygote, Humans, Immunohistochemistry, Interneurons, Neurons, Organ Size, Parvalbumins, Biomarkers, Gene Expression, Mice, Knockout, Gene Expression Profiling, Mice, Histone Acetyltransferases

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