title: Neuron-astrocyte signaling is preserved in the aging brain.
abstract: Astrocytes play crucial roles in brain homeostasis and are emerging as regulatory elements of neuronal and synaptic physiology by responding to neurotransmitters with Ca2+elevations and releasing gliotransmitters that activate neuronal receptors. Aging involves neuronal and astrocytic alterations, being considered risk factor for neurodegenerative diseases. Most evidence of the astrocyte-neuron signaling is derived from studies with young animals; however, the features of astrocyte-neuron signaling in adult and aging brain remain largely unknown. We have investigated the existence and properties of astrocyte-neuron signaling in physiologically and pathologically aging mouse hippocampal and cortical slices at different lifetime points (0.5 to 20 month-old animals). We found that astrocytes preserved their ability to express spontaneous and neurotransmitter-dependent intracellular Ca2+signals from juvenile to aging brains. Likewise, resting levels of gliotransmission, assessed by neuronal NMDAR activation by glutamate released from astrocytes, were largely preserved with similar properties in all tested age groups, but DHPG-induced gliotransmission was reduced in aged mice. In contrast, gliotransmission was enhanced in the APP/PS1 mouse model of Alzheimer's disease, indicating a dysregulation of astrocyte-neuron signaling in pathological conditions. Disruption of the astrocytic IP3R2 mediated-signaling, which is required for neurotransmitter-induced astrocyte Ca2+signals and gliotransmission, boosted the progression of amyloid plaque deposits and synaptic plasticity impairments in APP/PS1 mice at early stages of the disease. Therefore, astrocyte-neuron interaction is a fundamental signaling, largely conserved in the adult and aging brain of healthy animals, but it is altered in Alzheimer's disease, suggesting that dysfunctions of astrocyte Ca2+physiology may contribute to this neurodegenerative disease. GLIA 2017 GLIA 2017;65:569-580.
authors.affiliation: Instituto Cajal, CSIC, Madrid, 28002, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Gómez-Gonzalo
authors.affiliation: Department of Neuroscience, University of Minnesota, Minneapolis, 55455.
authors.forename: Mario
authors.initials: M
authors.lastname: Martin-Fernandez
authors.affiliation: Instituto Cajal, CSIC, Madrid, 28002, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Martínez-Murillo
authors.affiliation: Instituto Cajal, CSIC, Madrid, 28002, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Mederos
authors.affiliation: Instituto Cajal, CSIC, Madrid, 28002, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Hernández-Vivanco
authors.affiliation: Department of Neuroscience, University of Minnesota, Minneapolis, 55455.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Jamison
authors.affiliation: Instituto Cajal, CSIC, Madrid, 28002, Spain.
authors.forename: Ana P
authors.initials: AP
authors.lastname: Fernandez
authors.affiliation: Instituto Cajal, CSIC, Madrid, 28002, Spain.
authors.forename: Julia
authors.initials: J
authors.lastname: Serrano
authors.affiliation: Instituto Cajal, CSIC, Madrid, 28002, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Calero
authors.affiliation: College of Medicine, University of Florida, Gainesville, Florida, 32610-0261.
authors.forename: Hunter S
authors.initials: HS
authors.lastname: Futch
authors.affiliation: Aging and Neurodegeneration Unit, Biomedical Research Institute of Barcelona (IIBB), CSIC and IDIBAPS, Barcelona, 08036, Spain.
authors.forename: Rubén
authors.initials: R
authors.lastname: Corpas
authors.affiliation: Aging and Neurodegeneration Unit, Biomedical Research Institute of Barcelona (IIBB), CSIC and IDIBAPS, Barcelona, 08036, Spain.
authors.forename: Coral
authors.initials: C
authors.lastname: Sanfeliu
authors.affiliation: Instituto Cajal, CSIC, Madrid, 28002, Spain.
authors.forename: Gertrudis
authors.initials: G
authors.lastname: Perea
authors.affiliation: Department of Neuroscience, University of Minnesota, Minneapolis, 55455.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Araque
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000375:Aging; D016564:Amyloid beta-Protein Precursor / Q000172:deficiency / Q000235:genetics; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000166:cytology* / Q000254:growth & development; D002118:Calcium / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D053764:Presenilin-1 / Q000172:deficiency / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D055366:Synaptic Potentials / Q000187:drug effects / Q000235:genetics
chemical_list: D016564:Amyloid beta-Protein Precursor; D018683:Excitatory Amino Acid Agents; D053764:Presenilin-1; C580804:presenilin 1, mouse; D008734:Methoxyhydroxyphenylglycol; D000255:Adenosine Triphosphate; D000109:Acetylcholine; D002118:Calcium; C010117:3,4-dihydroxyphenylglycol
keywords: astrocytes; brain aging; gliotransmission; neuron-glia signaling; synaptic plasticity