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.

• Klíčová slova
• Anti-NMDAR encephalitis, BDNF, Dendritic branching, Neuronal development, Synaptic proteins,
• MeSH
• dendrity * účinky léků   metabolismus   MeSH
• krysa rodu Rattus MeSH
• kultivované buňky MeSH
• membránové proteiny metabolismus   imunologie   MeSH
• mozkový neurotrofický faktor * metabolismus   MeSH
• neurony * metabolismus   účinky léků   MeSH
• protein PSD-95 metabolismus   MeSH
• proteiny nervové tkáně imunologie   metabolismus   MeSH
• receptory N-methyl-D-aspartátu * imunologie   MeSH
• synaptofysin metabolismus   MeSH
• transportní proteiny MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• gephyrin MeSH Prohlížeč
• membránové proteiny MeSH
• mozkový neurotrofický faktor * MeSH
• protein PSD-95 MeSH
• proteiny nervové tkáně MeSH
• receptory N-methyl-D-aspartátu * MeSH
• synaptofysin MeSH
• transportní proteiny MeSH

NMDA receptors (NMDARs) comprise a subclass of neurotransmitter receptors whose surface expression is regulated at multiple levels, including processing in the endoplasmic reticulum (ER), intracellular trafficking via the Golgi apparatus, internalization, recycling, and degradation. With respect to early processing, NMDARs are regulated by the availability of GluN subunits within the ER, the presence of ER retention and export signals, and posttranslational modifications, including phosphorylation and palmitoylation. However, the role of N-glycosylation, one of the most common posttranslational modifications, in regulating NMDAR processing has not been studied in detail. Using biochemistry, confocal and electron microscopy, and electrophysiology in conjunction with a lentivirus-based molecular replacement strategy, we found that NMDARs are released from the ER only when two asparagine residues in the GluN1 subunit (Asn-203 and Asn-368) are N-glycosylated. Although the GluN2A and GluN2B subunits are also N-glycosylated, their N-glycosylation sites do not appear to be essential for surface delivery of NMDARs. Furthermore, we found that removing N-glycans from native NMDARs altered the receptor affinity for glutamate. Our results suggest a novel mechanism by which neurons ensure that postsynaptic membranes contain sufficient numbers of functional NMDARs.

• Klíčová slova
• endoplasmic reticulum (ER), glutamate receptor, glycosylation, neuron, synapse, trafficking,
• MeSH
• Cercopithecus aethiops MeSH
• COS buňky MeSH
• endoplazmatické retikulum metabolismus   MeSH
• glykosylace MeSH
• Golgiho aparát metabolismus   MeSH
• HEK293 buňky MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• N-methylaspartát chemie   metabolismus   MeSH
• nervový přenos * MeSH
• neurony chemie   metabolismus   MeSH
• polysacharidy metabolismus   MeSH
• receptory N-methyl-D-aspartátu chemie   metabolismus   MeSH
• synapse metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• N-methylaspartát MeSH
• polysacharidy MeSH
• receptory N-methyl-D-aspartátu MeSH