Cited by 1,344Neuroscience and Neuropharmacology ResearchNeuroinflammation and Neurodegeneration MechanismsGenetics and Neurodevelopmental Disorders

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Control of Synaptic Strength by Glial TNFα

Beattie, Eric C., Stellwagen, David, Morishita, Wade, Bresnahan, Jacqueline C., Ha, Byeong Keun, Von Zastrow, Mark, Beattie, Michael S., Malenka, Robert C.·2002·Science

DOI 10.1126/science.1067859

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Abstract

Activity-dependent modulation of synaptic efficacy in the brain contributes to neural circuit development and experience-dependent plasticity. Although glia are affected by activity and ensheathe synapses, their influence on synaptic strength has largely been ignored. Here, we show that a protein produced by glia, tumor necrosis factor alpha (TNFalpha), enhances synaptic efficacy by increasing surface expression of AMPA receptors. Preventing the actions of endogenous TNFalpha has the opposite effects. Thus, the continual presence of TNFalpha is required for preservation of synaptic strength at excitatory synapses. Through its effects on AMPA receptor trafficking, TNFalpha may play roles in synaptic plasticity and modulating responses to neural injury.

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Supplementary material is available on Science Online at www.sciencemag.org/cgi/content/full/295/5563/2282/DC1
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Authors: Beattie, E. C., Stellwagen, D., Morishita, W., Bresnahan, J. C., Ha, B. K., Von Zastrow, M., Beattie, M. S., & Malenka, R. C.
Affiliations: Stanford Medicine (US)
The Ohio State University Wexner Medical Center (US)
Departments of Psychiatry and Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143, USA.
Corresponding author: Beattie, Michael S.
Malenka, Robert C.
ORCID: Stellwagen, David
Bresnahan, Jacqueline C.
Beattie, Michael S.
Malenka, Robert C.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2002-03-22
Volume: 295
Issue: 5563
Pages: 2282-2285
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.1067859
OpenAlex: W1548862642
Cited by: 1,344
References: 22
Citations by year: 2026: 36 · 2025: 33 · 2024: 47 · 2023: 58 · 2022: 57 · 2021: 82 · 2020: 65 · 2019: 56 · 2018: 59 · 2017: 67 · 2016: 58 · 2015: 61 · 2014: 64 · 2013: 73 · 2012: 73
FWCI: 14.84
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Mental Health (MH 063394)
National Institute on Drug Abuse (DA 00439)
National Institute of Neurological Disorders and Stroke (NS38079, R01NS031193, R01NS038079, NS 31193)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords: synaptic efficacy, AMPA receptor trafficking, synaptic plasticity, excitatory synapses, nerve injury
MeSH terms: Animals, Astrocytes, Cells, Cultured, Gene Expression Regulation, Hippocampus, Synaptic Transmission, Neuronal Plasticity, Neurons, Synapses, Tumor Necrosis Factor-alpha, Antigens, CD, Culture Media, Conditioned, Rats, Sprague-Dawley, Receptors, AMPA, Receptors, Tumor Necrosis Factor, Receptors, Tumor Necrosis Factor, Type I, Rats

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Control of Synaptic Strength by Glial TNFα

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