title: Exocytosis of gliotransmitters from cortical astrocytes: implications for synaptic plasticity and aging.
abstract: Maintaining brain function during aging is very important for mental and physical health. Recent studies showed a crucial importance of communication between two major types of brain cells: neurons transmitting electrical signals, and glial cells, which maintain the well-being and function of neurons. Still, the study of age-related changes in neuron-glia signalling is far from complete. We have shown previously that cortical astrocytes are capable of releasing ATP by a quantal soluble N-ethylmaleimide-sensitive factor-attachment protein receptor (SNARE) complex-dependent mechanism. Release of ATP from cortical astrocytes can be activated via various pathways, including direct UV-uncaging of intracellular Ca²⁺ or G-protein-coupled receptors. Importantly, release of both ATP and glutamate from neocortical astrocytes was not observed in brain slices of dominant-negative SNARE (dnSNARE) mice, expressing dnSNARE domain selectively in astrocytes. We also discovered that astrocyte-driven ATP can cause significant attenuation of synaptic inhibition in the pyramidal neurons via Ca²⁺-interaction between the neuronal ATP and γ-aminobutyric acid (GABA) receptors. Furthermore, we showed that astrocyte-derived ATP can facilitate the induction of long-term potentiation of synaptic plasticity in the neocortex. Our recent data have shown that an age-related decrease in the astroglial Ca²⁺ signalling can cause a substantial decrease in the exocytosis of gliotransmitters, in particular ATP. Age-related impairment of ATP release from cortical astrocytes can cause a decrease in the extent of astroglial modulation of synaptic transmission in the neocortex and can therefore contribute to the age-related impairment of synaptic plasticity and cognitive decline. Combined, our results strongly support the physiological relevance of glial exocytosis for glia-neuron communications and brain function.
authors.affiliation: *School of Life Sciences, University of Warwick, Coventry CV4 7AL, U.K.
authors.forename: Ulyana
authors.initials: U
authors.lastname: Lalo
authors.affiliation: *School of Life Sciences, University of Warwick, Coventry CV4 7AL, U.K.
authors.forename: Seyed
authors.initials: S
authors.lastname: Rasooli-Nejad
authors.affiliation: *School of Life Sciences, University of Warwick, Coventry CV4 7AL, U.K.
authors.forename: Yuriy
authors.initials: Y
authors.lastname: Pankratov
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000375:Aging; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D020013:Calcium Signaling; D002450:Cell Communication; D005089:Exocytosis; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D019579:Neocortex / Q000166:cytology / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009473:Neuronal Plasticity; D050600:SNARE Proteins / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission
chemical_list: D009419:Nerve Tissue Proteins; D050600:SNARE Proteins; D018698:Glutamic Acid; D000255:Adenosine Triphosphate