Impaired functional connectivity of the hippocampus in translational murine models of NMDA-receptor antibody associated neuropsychiatric pathology.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
24 Oct 2023
24 Oct 2023
Historique:
received:
10
10
2022
accepted:
11
10
2023
revised:
28
09
2023
medline:
25
10
2023
pubmed:
25
10
2023
entrez:
24
10
2023
Statut:
aheadofprint
Résumé
Decreased hippocampal connectivity and disruption of functional networks are established resting-state functional MRI (rs-fMRI) features that are associated with neuropsychiatric symptom severity in human anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. However, the underlying pathophysiology of NMDAR encephalitis remains poorly understood. Application of patient-derived monoclonal antibodies against the NR1 (GluN1) subunit of the NMDAR now allows for the translational investigation of functional connectivity in experimental murine NMDAR antibody disease models with neurodevelopmental disorders. Using rs-fMRI, we studied functional connectivity alterations in (1) adult C57BL/6 J mice that were intrathecally injected with a recombinant human NR1 antibody over 14 days (n = 10) and in (2) a newly established mouse model with in utero exposure to a human recombinant NR1 antibody (NR1-offspring) at the age of (2a) 8 weeks (n = 15) and (2b) 10 months (n = 14). Adult NR1-antibody injected mice showed impaired functional connectivity within the left hippocampus compared to controls, resembling impaired connectivity patterns observed in human NMDAR encephalitis patients. Similarly, NR1-offspring showed significantly reduced functional connectivity in the hippocampus after 8 weeks, and impaired connectivity in the hippocampus was likewise observed in NR1-offspring at the age of 10 months. We successfully reproduced functional connectivity changes within the hippocampus in different experimental murine systems that were previously observed in human NMDAR encephalitis patients. Translational application of this method within a combined imaging and histopathological framework will allow future experimental studies to identify the underlying biological mechanisms and may eventually facilitate non-invasive monitoring of disease activity and treatment responses in autoimmune encephalitis.
Identifiants
pubmed: 37875549
doi: 10.1038/s41380-023-02303-9
pii: 10.1038/s41380-023-02303-9
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023. The Author(s).
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