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

The tripartite synapse: roles for gliotransmission in health and disease

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

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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Crossref · 10.1016/j.molmed.2006.12.005

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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

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