Academic Journal
Novel players in the aging synapse: impact on cognition
| العنوان: | Novel players in the aging synapse: impact on cognition |
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| المؤلفون: | Temido Ferreira, Mariana, Coelho, Joana E, Pousinha, Paula, Lopes, Luisa V. |
| المساهمون: | Repositório da Universidade de Lisboa |
| بيانات النشر: | Mary Ann Liebert, Inc., 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | NMDA receptor, Adenosine A2A receptor, Aging, Hippocampus, mGluR5 receptor, Memory, Synaptic plasticity |
| الوصف: | © Mariana Temido-Ferreira, et al. 2019; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons Attribution Noncommercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are cited. |
| Description (Translated): | While neuronal loss has long been considered as the main contributor to age-related cognitive decline, these alterations are currently attributed to gradual synaptic dysfunction driven by calcium dyshomeostasis and alterations in ionotropic/metabotropic receptors. Given the key role of the hippocampus in encoding, storage, and retrieval of memory, the morpho- and electrophysiological alterations that occur in the major synapse of this network-the glutamatergic-deserve special attention. We guide you through the hippocampal anatomy, circuitry, and function in physiological context and focus on alterations in neuronal morphology, calcium dynamics, and plasticity induced by aging and Alzheimer's disease (AD). We provide state-of-the art knowledge on glutamatergic transmission and discuss implications of these novel players for intervention. A link between regular consumption of caffeine-an adenosine receptor blocker-to decreased risk of AD in humans is well established, while the mechanisms responsible have only now been uncovered. We review compelling evidence from humans and animal models that implicate adenosine A2A receptors (A2AR) upsurge as a crucial mediator of age-related synaptic dysfunction. The relevance of this mechanism in patients was very recently demonstrated in the form of a significant association of the A2AR-encoding gene with hippocampal volume (synaptic loss) in mild cognitive impairment and AD. Novel pathways implicate A2AR in the control of mGluR5-dependent NMDAR activation and subsequent Ca2+ dysfunction upon aging. The nature of this receptor makes it particularly suited for long-term therapies, as an alternative for regulating aberrant mGluR5/NMDAR signaling in aging and disease, without disrupting their crucial constitutive activity. M.T.-F. and J.E.C. were supported by a fellowship from Fundação para a Ciência e Tecnologia (FCT, Portugal); L.V.L is an Investigator CEEC-FCT. P.A.P. is supported by EU Joint Program—Neurodegenerative Disease Research (JPND) project CIRCPROT (jointly funded by BMBF, MIUR, and EU Horizon 2020 grant agreement no. 643417). This study was also funded by Santa Casa da Misericórdia - Mantero Belard 2018 (MB-7-2018) and by UID/BIM/50005/2019, project funded by Fundação para a Ciência e a Tecnologia (FCT)/ Ministério da Ciência, Tecnologia e Ensino Superior (MCTES) through Fundos do Orçamento de Estado. |
| نوع الوثيقة: | journal article |
| وصف الملف: | application/pdf |
| اللغة: | English |
| Relation: | J Caffeine Adenosine Res. 2019 Sep 1;9(3):104-127; 2573-3397; 2573-3400 |
| DOI: | 10.1089/caff.2019.0013 |
| الاتاحة: | http://hdl.handle.net/10451/55379 |
| Rights: | open access |
| رقم الانضمام: | rcaap.com.ul.repositorio.ul.pt.10451.55379 |
| قاعدة البيانات: | RCAAP |
| DOI: | 10.1089/caff.2019.0013 |
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