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Immuno-Pharmacological Characterization of Presynaptic GluN3A-Containing NMDA Autoreceptors: Relevance to Anti-NMDA Receptor Autoimmune Diseases
- Source :
- Molecular neurobiology 56 (2019): 6142–6155. doi:10.1007/s12035-019-1511-8, info:cnr-pdr/source/autori:Olivero G, Vergassola M, Cisani F, Usai C, Pittaluga A/titolo:Immuno-Pharmacological Characterization of Presynaptic GluN3A-Containing NMDA Autoreceptors: Relevance to Anti-NMDA Receptor Autoimmune Diseases/doi:10.1007%2Fs12035-019-1511-8/rivista:Molecular neurobiology/anno:2019/pagina_da:6142/pagina_a:6155/intervallo_pagine:6142–6155/volume:56
- Publication Year :
- 2019
- Publisher :
- Humana Press, Clifton, NJ , Stati Uniti d'America, 2019.
-
Abstract
- Mouse hippocampal glutamatergic nerve endings express presynaptic release-regulating NMDA autoreceptors (NMDARs). The presence of GluN1, GluN2A, GluN2B, and GluN3A subunits in hippocampal vesicular glutamate transporter type 1-positive synaptosomes was confirmed with confocal microscopy. GluN2C, GluN2D, and GluN3B immunopositivity was scarcely present. Incubation of synaptosomes with the anti-GluN1, the anti-GluN2A, the anti-GluN2B, or the anti-GluN3A antibody prevented the 30 mu M NMDA/1 mu M glycine-evoked [H-3]d-aspartate ([H-3]d-ASP) release. The NMDA/glycine-evoked [H-3]d-ASP release was reduced by increasing the external protons, consistent with the participation of GluN1 subunits lacking the N1 cassette to the receptor assembly. The result also excludes the involvement of GluN1/GluN3A dimers into the NMDA-evoked overflow. Complement (1:300) released [H-3]d-ASP in a dizocilpine-sensitive manner, suggesting the participation of a NMDAR-mediated component in the releasing activity. Accordingly, the complement-evoked glutamate overflow was reduced in anti-GluN-treated synaptosomes when compared to the control. We speculated that incubation with antibodies had favored the internalization of NMDA receptors. Indeed, a significant reduction of the GluN1 and GluN2B proteins in the plasma membranes of anti-GluN1 or anti-GluN2B antibody-treated synaptosomes emerged in biotinylation studies. Altogether, our findings confirm the existence of presynaptic GluN3A-containing release-regulating NMDARs in mouse hippocampal glutamatergic nerve endings. Furthermore, they unveil presynaptic alteration of the GluN subunit insertion in synaptosomal plasma membranes elicited by anti-GluN antibodies that might be relevant to the central alterations occurring in patients suffering from autoimmune anti-NMDA diseases.
- Subjects :
- 0301 basic medicine
media_common.quotation_subject
GluN3
Neuroscience (miscellaneous)
Presynaptic Terminals
Complement
Glutamic Acid
Hippocampal formation
Tritium
Hippocampus
Receptors, N-Methyl-D-Aspartate
Antibodies
Autoimmune Diseases
Potassium Chloride
03 medical and health sciences
Cellular and Molecular Neuroscience
Glutamatergic
0302 clinical medicine
Animals
Internalization
Receptor
Presynaptic NMDA autoreceptor
Anti-GluN antibody
media_common
Aspartic Acid
Chemistry
Glutamate receptor
NMDA internalization
Neurology
Hydrogen-Ion Concentration
Cell biology
Mice, Inbred C57BL
Protein Subunits
030104 developmental biology
nervous system
Autoreceptor
NMDA receptor
Free nerve ending
030217 neurology & neurosurgery
Synaptosomes
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Molecular neurobiology 56 (2019): 6142–6155. doi:10.1007/s12035-019-1511-8, info:cnr-pdr/source/autori:Olivero G, Vergassola M, Cisani F, Usai C, Pittaluga A/titolo:Immuno-Pharmacological Characterization of Presynaptic GluN3A-Containing NMDA Autoreceptors: Relevance to Anti-NMDA Receptor Autoimmune Diseases/doi:10.1007%2Fs12035-019-1511-8/rivista:Molecular neurobiology/anno:2019/pagina_da:6142/pagina_a:6155/intervallo_pagine:6142–6155/volume:56
- Accession number :
- edsair.doi.dedup.....107519d7d03476728cc6772ed11161d4