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| Pàgina inicial > Articles > Articles publicats > Placental transfer of NMDAR antibodies causes reversible alterations in mice |
(Institut d'Investigacions Biomèdiques August Pi i Sunyer) (Institut d'Investigacions Biomèdiques August Pi i Sunyer) (Universitat Autònoma de Barcelona. Departament de Pediatria, Obstetrícia i Ginecologia i Medicina Preventiva i Salut Pública) (Institut d'Investigacions Biomèdiques August Pi i Sunyer) (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
| Data: | 2021 |
| Resum: | To determine whether maternofetal transfer of NMDA receptor (NMDAR) antibodies has pathogenic effects on the fetus and offspring, we developed a model of placental transfer of antibodies. Pregnant C57BL/6J mice were administered via tail vein patients' or controls' immunoglobulin G (IgG) on days 14-16 of gestation, when the placenta is able to transport IgG and the immature fetal blood-brain barrier is less restrictive to IgG crossing. Immunohistochemical and DiOlistic (gene gun delivery of fluorescent dye) staining, confocal microscopy, standardized developmental and behavioral tasks, and hippocampal long-term potentiation were used to determine the antibody effects. In brains of fetuses, patients' IgG, but not controls' IgG, bound to NMDAR, causing a decrease in NMDAR clusters and cortical plate thickness. No increase in neonatal mortality was observed, but offspring exposed in utero to patients' IgG had reduced levels of cell-surface and synaptic NMDAR, increased dendritic arborization, decreased density of mature (mushroom-shaped) spines, microglial activation, and thinning of brain cortical layers II-IV with cellular compaction. These animals also had a delay in innate reflexes and eye opening and during follow-up showed depressive-like behavior, deficits in nest building, poor motor coordination, and impaired social-spatial memory and hippocampal plasticity. Remarkably, all these paradigms progressively improved (becoming similar to those of controls) during follow-up until adulthood. In this model, placental transfer of patients' NMDAR antibodies caused severe but reversible synaptic and neurodevelopmental alterations. Reversible antibody effects may contribute to the infrequent and limited number of complications described in children of patients who develop anti-NMDAR encephalitis during pregnancy. |
| Ajuts: | Instituto de Salud Carlos III 17/00234 Ministerio de Economía y Competitividad RTI2018-094374-B-I00 Agència de Gestió d'Ajuts Universitaris i de Recerca 2018FI_B_00487 Agència de Gestió d'Ajuts Universitaris i de Recerca 2019FI_B1 00212 |
| Nota: | Altres ajuts: Project Integrative of Excellence (PIE 16/00014); Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER; #CB15/00010); "La Caixa" Foundation (ID 100010434, under the agreement LCF/PR/HR17/52150001); The Safra Foundation (J.D.), and Fundació CELLEX (J.D.); Centres de Recerca de Catalunya (CERCA) program by La Generalitatde Catalunya (J.R.); Pla Estratègic de Recerca i Innovació en Salut (PERIS, SLT002/16/00346, J.P.); Basque Government Doctoral Fellowship Program (PRE_ 2019_1_0255; E.M.) |
| Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.  |
| Llengua: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Publicat a: | Neurology® neuroimmunology & neuroinflammation, Vol. 8 Núm. 1 (january 2021) , ISSN 2332-7812 |
