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Contribution of Astrocyte Glutamate Release to Excitotoxicity

  • Daniela Rossi
  • Paola Bezzi
  • Maria Domercq
  • Liliana Brambilla
  • Jacopo Meldolesi
  • Andrea Volterra

Abstract

Although glial cells have been traditionally viewed as supportive partners of neurons, recent studies demonstrated that astrocytes possess functional receptors and are able to release transmitters by regulated pathways. Astrocytes were found to react to synaptically released neurotransmitters by undergoing intracellular calcium elevation which subsequently triggers an exocytosis-like glial transmitter release. These findings led to a new concept of neuron-glia intercommunication where astrocytes play an unsuspected dynamic role by integrating neuronal inputs and modulating synaptic activity. The discovery that glial release of the excitatory amino acid glutamate is controlled by molecules linked to inflammatory functions, such as cytokines and prostaglandins, suggested that glia-to-neuron signalling may be implicated in physiological processes but also in pathological situations. Indeed, a local and parenchimal inflammatory reaction characterised by astroglia and microglia activation has been reported in several brain pathologies including prion diseases and various dementias like Alzheimer’s disease and the AIDS dementia complex. In agreement, stimulation of the calcium-dependent glial glutamate release process via activation of the chemokine receptor, CXCR4, by its natural ligand, SDF1α, is crucial for normal brain communication. However, the interaction of the same receptor with the HIV-1 coat protein gp120 in pathological conditions caused deregulation of the glutamate system and excitotoxic neuronal cell death. The findings herein reported suggest that a better comprehension of the glial-neuron glutamatergic interplay may provide information about nonnal brain functions and may highlight possible molecular targets for therapeutical interventions in pathology.

Keywords

astrocytes glutamate release excitotoxicity glial signalling calcium 

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Copyright information

© Springer Science+Business Media New York 2004

Authors and Affiliations

  • Daniela Rossi
    • 1
  • Paola Bezzi
    • 1
    • 2
  • Maria Domercq
    • 1
  • Liliana Brambilla
    • 1
  • Jacopo Meldolesi
    • 3
  • Andrea Volterra
    • 1
    • 2
  1. 1.Department of Pharmacological Sciences and Center of Excellence on Neurodegenerative DiseasesUniversity of MilanMilanItaly
  2. 2.Institute of Cell Biology and MorphologyUniversity of LausanneLausanneSwitzerland
  3. 3.Department of NeuroscienceVita-Salute San Raffaele University and Excellence Centre in Cell DifferentiationMilanItaly

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