Mapping brain networks in MPS I mice and their restoration following gene therapy.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
05 08 2023
Historique:
received: 09 02 2023
accepted: 02 08 2023
medline: 7 8 2023
pubmed: 6 8 2023
entrez: 5 8 2023
Statut: epublish

Résumé

Mucopolysaccharidosis type I (MPS I) is an inherited lysosomal disorder that causes syndromes characterized by physiological dysfunction in many organs and tissues. Despite the recognizable morphological and behavioral deficits associated with MPS I, neither the underlying alterations in functional neural connectivity nor its restoration following gene therapy have been shown. By employing high-resolution resting-state fMRI (rs-fMRI), we found significant reductions in functional neural connectivity in the limbic areas of the brain that play key roles in learning and memory in MPS I mice, and that adeno-associated virus (AAV)-mediated gene therapy can reestablish most brain connectivity. Using logistic regression in MPS I and treated animals, we identified functional networks with the most alterations. The rs-fMRI and statistical methods should be translatable into clinical evaluation of humans with neurological disorders.

Identifiants

pubmed: 37543633
doi: 10.1038/s41598-023-39939-0
pii: 10.1038/s41598-023-39939-0
pmc: PMC10404260
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

12716

Subventions

Organisme : NIBIB NIH HHS
ID : U01 EB026978
Pays : United States
Organisme : NIH HHS
ID : R01 NS118330
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS133006
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH111413
Pays : United States
Organisme : NIBIB NIH HHS
ID : P41 EB027061
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS118330
Pays : United States

Informations de copyright

© 2023. Springer Nature Limited.

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Auteurs

Wei Zhu (W)

Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, 55455, USA.
Department of Radiology, University of Minnesota, Minneapolis, MN, 55455, USA.

Li Ou (L)

Department of Pediatrics, University of Minnesota, Minneapolis, MN, 55455, USA.
Genemagic Biosciences, Media, PA, 19063, USA.

Lin Zhang (L)

Division of Biostatistics, University of Minnesota, Minneapolis, MN, 55455, USA.

Isaac H Clark (IH)

Biomedical Engineering Graduate Program, University of Minnesota, Minneapolis, MN, 55455, USA.

Ying Zhang (Y)

Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN, 55455, USA.

Xiao-Hong Zhu (XH)

Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, 55455, USA.
Department of Radiology, University of Minnesota, Minneapolis, MN, 55455, USA.

Chester B Whitley (CB)

Department of Pediatrics, University of Minnesota, Minneapolis, MN, 55455, USA.

Perry B Hackett (PB)

Department of Genetics, Cell Biology Development, University of Minnesota, Minneapolis, MN, 55455, USA.
Stem Cell Institute, University of Minnesota, Minneapolis, MN, 55455, USA.

Walter C Low (WC)

Biomedical Engineering Graduate Program, University of Minnesota, Minneapolis, MN, 55455, USA. lowwalt@umn.edu.
Stem Cell Institute, University of Minnesota, Minneapolis, MN, 55455, USA. lowwalt@umn.edu.
Department of Neurosurgery, University of Minnesota, Minneapolis, MN, 55455, USA. lowwalt@umn.edu.
Graduate Program in Neuroscience, University of Minnesota, Minneapolis, MN, 55455, USA. lowwalt@umn.edu.

Wei Chen (W)

Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, 55455, USA. chenx075@umn.edu.
Department of Radiology, University of Minnesota, Minneapolis, MN, 55455, USA. chenx075@umn.edu.
Biomedical Engineering Graduate Program, University of Minnesota, Minneapolis, MN, 55455, USA. chenx075@umn.edu.
Stem Cell Institute, University of Minnesota, Minneapolis, MN, 55455, USA. chenx075@umn.edu.

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