Brain-derived Neurotrophic Factor Regulates the Expression and Synaptic Delivery ofα-Amino-3-hydroxy-5-methyl-4-isoxazole Propionic Acid Receptor Subunits in Hippocampal Neurons
Open accessAbstract
Brain-derived neurotrophic factor (BDNF) plays an important role in synaptic plasticity in the hippocampus, but the mechanisms involved are not fully understood. The neurotrophin couples synaptic activation to changes in gene expression underlying long term potentiation and short term plasticity. Here we show that BDNF acutely up-regulates GluR1, GluR2, and GluR3 alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunits in 7-day in vitro cultured hippocampal neurons. The increase in GluR1 and GluR2 protein levels in developing cultures was impaired by K252a, a tropomyosin-related [corrected] kinase (Trk) inhibitor, and by translation (emetine and anisomycin) and transcription (alpha-amanitine and actinomycin D) inhibitors [corrected] The increase in GluR1 and GluR2 protein levels in developing cultures was impaired by K252a, a Trk inhibitor, and by translation (emetine and anisomycin) and transcription (alpha-amanitine and actinomycin D) inhibitors. Accordingly, BDNF increased the mRNA levels for GluR1 and GluR2 subunits. Biotinylation studies showed that stimulation with BDNF for 30 min selectively increased the amount of GluR1 associated with the plasma membrane, and this effect was abrogated by emetine. Under the same conditions, BDNF induced GluR1 phosphorylation on Ser-831 through activation of protein kinase C and Ca(2+)-calmodulin-dependent protein kinase II. Chelation of endogenous extracellular BDNF with TrkB-IgG selectively decreased GluR1 protein levels in 14-day in vitro cultures of hippocampal neurons. Moreover, BDNF promoted synaptic delivery of homomeric GluR1 AMPA receptors in cultured organotypic slices, by a mechanism independent of NMDA receptor activation. Taken together, the results indicate that BDNF up-regulates the protein levels of AMPA receptor subunits in hippocampal neurons and induces the delivery of AMPA receptors to the synapse.
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BDNF increases AMPA responses by enhancing AMPA receptor translation and cell surface expression.
“BDNF has been shown to increase α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) responses by enhancing AMPA receptor translation and cell surface expression (Caldeira et al., 2007; Fortin et al., 2012).”
From BDNF - a key transducer of antidepressant effects (2016) · cites this paper as Caldeira et al., 2007
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- Authors
- Caldeira, M. V., Melo, C. V., Pereira, D. B., Carvalho, R., Correia, S. S., Backos, D. S., Carvalho, A. L., Esteban, J. A., & Duarte, C. B.
- Affiliations
- Centro de Neurociências e Biologia Celular (PT)
- University of Michigan (US)
- Corresponding author
- Duarte, Carlos B.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2007-04
- Volume
- 282
- Issue
- 17
- Pages
- 12619-12628
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2011148606
- Cited by
- 251
- References
- 8
- Citations by year
- 2026: 10 · 2025: 6 · 2024: 6 · 2023: 14 · 2022: 19 · 2021: 11 · 2020: 11 · 2019: 7 · 2018: 16 · 2017: 12 · 2016: 17 · 2015: 9 · 2014: 14 · 2013: 23 · 2012: 21
- FWCI
- 5.71
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Funders
- Regeneron Pharmaceuticals
- Universidade de Coimbra
- European Regional Development Fund
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- brain-derived neurotrophic factor, AMPA receptor subunits, GluR1, GluR2, GluR3, hippocampal neurons, synaptic plasticity, TrkB receptor, protein kinase C, CaMKII, receptor phosphorylation, organotypic slice cultures
- MeSH terms
- Animals, Cells, Cultured, Hippocampus, Immunoglobulin G, Neurons, Phosphorylation, Protein Kinase C, Protein Processing, Post-Translational, Recombinant Fusion Proteins, Up-Regulation, Rats, Wistar, Calcium-Calmodulin-Dependent Protein Kinases, Receptors, AMPA, Brain-Derived Neurotrophic Factor, Receptor, trkB, Protein Transport, Chromosome Pairing, Rats
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