J Appl Biomed 22:136-140, 2024 | DOI: 10.32725/jab.2024.019

Anti-NMDAR1 antibody impairs dendritic branching in immature cultured neurons

Pascal Jorratt^{1, 2, *}, Aneta Petrušková^{1, 2, 3}

¹ National Institute of Mental Health, Klecany, Czech Republic

² Charles University, Third Faculty of Medicine, Prague, Czech Republic

³ Friedrich-Alexander Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Department of Psychiatry and Psychotherapy, Erlangen, Germany

Anti-N-methyl D-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune disorder characterized by IgG antibodies targeting NMDAR. The prevalence is remarkably higher in women and some develop the condition during pregnancy. While immunotherapies have shown good outcomes for pregnant mothers and their infants, the impact on early neurodevelopment remains elusive. This study investigates the effects of anti-NMDAR antibody on the development of primary cortical cultures. Anti-NMDAR antibody was administered to the cultures at day in vitro 5 for the following 5 days to assess dendritic branching and arbor complexity, and at day in vitro 14 for measuring the expression of brain-derived neurotrophic factor (BDNF) and synaptic proteins. Immature cultured neurons treated with anti-NMDAR antibody exhibited impaired dendritic branching and arbor complexity. Interestingly, BDNF expression was unaffected in mature neurons. Additionally, GluN1 expression, a mandatory NMDAR subunit, was significantly reduced, while no significant alterations were observed in PSD-95, gephyrin and synaptophysin expression. These findings shed light on the structural and synaptic impacts of anti-NMDAR antibody on immature neurons, providing evidence for their consequences in early neuronal development.

Keywords: Anti-NMDAR encephalitis; BDNF; Dendritic branching; Neuronal development; Synaptic proteins

Grants and funding:

This study was supported by GAUK 365121 (Charles University Grant Agency), NIMH (National Institute of Mental Health) Internal Grant 333 and Charles University research program Cooperatio-Neurosciences.

Conflicts of interest:

The authors have no conflict of interest to declare.

Received: April 4, 2024; Revised: July 2, 2024; Accepted: August 20, 2024; Prepublished online: September 19, 2024; Published: September 26, 2024  Show citation