Journal Article

DZNE-2026-00309

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png In utero exposure to NMDA receptor autoantibodies disrupts hippocampal circuit maturation.

Majoros, M. ; Zhang, C. ; Rahmati, V. ; Graf, J. ; Heckmann, M. ; Geis, C. ; Kreye, J.DZNE* ; Kaindl, A. M. ; Prüss, H.DZNE* ; Holthoff, K. ; Kirmse, K.

2026
Cell Press Maryland Heights, MO

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Please use a persistent id in citations: doi:10.1016/j.celrep.2026.117022

Abstract: Maternal anti-neuronal autoantibodies (ABs) have been linked to abnormal brain maturation and may increase the risk of neurodevelopmental disorders, yet their pathogenetic mechanisms remain elusive. Here, we show that in utero exposure to ABs targeting the NR1 subunit of N-methyl-D-aspartate (NMDA) receptors (NR1 ABs) disrupts hippocampal circuit maturation in mice. Using a passive-transfer model, we find that transplacental NR1 ABs impair GABAergic transmission in CA1 pyramidal cells (PCs) ex vivo. Ca2+ imaging and computational modeling reveal that this deficit compromises early synchronized network activity in neonatal CA1. In vivo, NR1 ABs hinder the emergence of continuous activity around eye opening-a critical milestone for later cognitive function-by reducing the ability of CA1 PCs to developmentally decouple from local network dynamics. Our findings implicate NR1 ABs as drivers of a developing hippocampal circuitopathy and highlight disrupted activity-dependent circuit refinement as a mechanistic link between maternal autoimmunity and neurodevelopmental dysfunction.

Keyword(s): Animals (MeSH) ; Receptors, N-Methyl-D-Aspartate: immunology (MeSH) ; Female (MeSH) ; Autoantibodies: immunology (MeSH) ; Pregnancy (MeSH) ; Mice (MeSH) ; Hippocampus: immunology (MeSH) ; Hippocampus: growth & development (MeSH) ; Pyramidal Cells: metabolism (MeSH) ; Prenatal Exposure Delayed Effects: immunology (MeSH) ; Mice, Inbred C57BL (MeSH) ; Male (MeSH) ; CA1 Region, Hippocampal (MeSH) ; CP: immunology ; CP: neuroscience ; NMDA receptor autoantibodies ; development ; in vivo ; neuronal circuits ; patch clamp ; two-photon imaging ; Receptors, N-Methyl-D-Aspartate ; Autoantibodies ; NR1 NMDA receptor

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Contributing Institute(s):

1. Autoimmune Encephalopathies (AG Prüß)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2026

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Database coverage:
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