Cited by 856Neuroscience and Neuropharmacology ResearchNeuroinflammation and Neurodegeneration MechanismsAmino Acid Enzymes and Metabolism

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The tripartite synapse: roles for gliotransmission in health and disease

Halassa, Michael M., Fellin, Tommaso, Haydon, Philip G.·2007·Trends in Molecular Medicine

DOI 10.1016/j.molmed.2006.12.005

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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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Authors: Halassa, M. M., Fellin, T., & Haydon, P. G.
Affiliations: University of Pennsylvania (US)
ORCID: Halassa, Michael M.
Fellin, Tommaso
Haydon, Philip G.
Venue: Trends in Molecular Medicine
Publisher: Elsevier BV
Published: 2007-02
Volume: 13
Issue: 2
Pages: 54-63
ISSN: 1471-4914 (ISSN-L)
DOI: 10.1016/j.molmed.2006.12.005
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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

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The tripartite synapse: roles for gliotransmission in health and disease

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