Academic Journal
Age‐dependent NMDA receptor function is regulated by the amyloid precursor protein
| العنوان: | Age‐dependent NMDA receptor function is regulated by the amyloid precursor protein |
|---|---|
| المؤلفون: | Rajão‐saraiva, Joana, Dunot, Jade, Ribera, Aurore, Temido‐ferreira, Mariana, Coelho, Joana, E, König, Svenja, Moreno, Sébastien, Enguita, Francisco, J, Willem, Michael, Kins, Stefan, Marie, Hélène, Lopes, Luísa Vaqueiro, Pousinha, Paula |
| المساهمون: | Universidade de Lisboa = University of Lisbon = Université de Lisbonne (ULISBOA), Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (1965 - 2019) (UNS)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UniCA), Ludwig Maximilian University Munich = Ludwig Maximilians Universität München (LMU), University of Kaiserslautern Kaiserslautern, ANR-22-CE37-0017,HACAP,Le circuit Hippocampe-Accumbens dans le vieillissement: démêler la physiologie de l'APP(2022) |
| المصدر: | ISSN: 1474-9718. |
| بيانات النشر: | HAL CCSD Wiley Open Access |
| سنة النشر: | 2023 |
| المجموعة: | HAL Université Côte d'Azur |
| مصطلحات موضوعية: | [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.BDD]Life Sciences [q-bio]/Development Biology |
| الوصف: | International audience ; N-methyl-D-aspartate receptors (NMDARs) are critical for the maturation and plasticity of glutamatergic synapses. In the hippocampus, NMDARs mainly contain GluN2A and/or GluN2B regulatory subunits. The amyloid precursor protein (APP) has emerged as a putative regulator of NMDARs, but the impact of this interaction to their function is largely unknown. By combining patch-clamp electrophysiology and molecular approaches, we unravel a dual mechanism by which APP controls GluN2B-NMDARs, depending on the life stage. We show that APP is highly abundant specifically at the postnatal post-synapse. It interacts with GluN2B-NMDARs, controlling its synaptic content and mediated currents, both in infant mice and primary neuronal cultures. Upon aging, the APP amyloidogenic derived C-terminal fragments, rather than APP full-length, contribute to aberrant GluN2B-NMDAR currents. Accordingly, we found that the APP processing is increased upon aging, both in mice and human brain. Interfering with stability or production of the APP intracellular domain normalized the GluN2B-NMDARs currents. While the first mechanism might be essential for synaptic maturation during development, the latter could contribute to age-related synaptic impairments. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | hal-04071447; https://hal.science/hal-04071447; https://hal.science/hal-04071447/document; https://hal.science/hal-04071447/file/Age%E2%80%90dependent%20NMDA%20receptor%20function%20is%20regulated%20by%20the%20amyloid%20precursor%20protein.pdf |
| DOI: | 10.1111/acel.13778 |
| الاتاحة: | https://hal.science/hal-04071447 https://hal.science/hal-04071447/document https://hal.science/hal-04071447/file/Age%E2%80%90dependent%20NMDA%20receptor%20function%20is%20regulated%20by%20the%20amyloid%20precursor%20protein.pdf https://doi.org/10.1111/acel.13778 |
| Rights: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.CE8875C5 |
| قاعدة البيانات: | BASE |
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