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The tripartite synapse: roles for gliotransmission in health and disease
Abstract
In addition to being essential supporters of neuronal function, astrocytes are now recognized as active elements in the brain. Astrocytes sense and integrate synaptic activity and, depending on intracellular Ca(2+) levels, release gliotransmitters (e.g. glutamate, d-serine and ATP) that have feedback actions on neurons. Recent experimental results have raised the possibility that quantitative variations in gliotransmission might contribute to disorders of the nervous system. Here, we discuss targeted molecular genetic approaches that have demonstrated that alterations in protein expression in astrocytes can lead to serious changes in neuronal function. We also introduce the concept of 'astrocyte activation spectrum' in which enhanced and reduced gliotransmission might contribute to epilepsy and schizophrenia, respectively. The results of future experimental tests of the astrocyte activation spectrum, which relates gliotransmission to neurological and psychiatric disorders, might point to a new therapeutic target in the brain.
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“Glial/CSPG cluster abnormalities may thus represent a contributing factor to dysregulated glutamatergic transmission, and more broadly to neuron/glia interactions, in major psychoses.15, 22, 105, 106”
From Aggrecan and chondroitin-6-sulfate abnormalities in schizophrenia and bipolar disorder: a postmortem study on the amygdala (2015) · cites this paper as [22]
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Metadata
- Authors
- Halassa, M. M., Fellin, T., & Haydon, P. G.
- Affiliations
- University of Pennsylvania (US)
- Venue
- Trends in Molecular Medicine
- Publisher
- Elsevier BV
- Published
- 2007-02
- Volume
- 13
- Issue
- 2
- Pages
- 54-63
- ISSN
- 1471-4914 (ISSN-L)
- OpenAlex
- W1977294596
- Cited by
- 852
- References
- 94
- Citations by year
- 2026: 17 · 2025: 23 · 2024: 30 · 2023: 26 · 2022: 39 · 2021: 68 · 2020: 44 · 2019: 33 · 2018: 45 · 2017: 34 · 2016: 71 · 2015: 52 · 2014: 50 · 2013: 57 · 2012: 56
- FWCI
- 4.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Molecular Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Epilepsy Society
- Epilepsy Foundation
- National Institute of Neurological Disorders and Stroke
- UCB Pharma
- 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 › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- gliotransmission, astrocytes, glutamate release, D-serine, ATP release, intracellular calcium, synaptic activity, epilepsy, schizophrenia, neurological disorders, mental illness, therapeutic target
- MeSH terms
- Adenosine Triphosphate, Animals, Astrocytes, Epilepsy, Humans, Models, Neurological, Synaptic Transmission, Neuronal Plasticity, Schizophrenia, Spinal Cord Injuries, Synapses, Receptors, N-Methyl-D-Aspartate, Neurotransmitter Agents, Glutamic Acid, Calcium Signaling
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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