Neuron–astrocyte signaling is preserved in the aging brain

Marta Gómez-Gonzalo, Mario Martin-Fernandez, Ricardo Martínez-Murillo, Sara Mederos, Alicia Hernández-Vivanco, Stephanie Jamison, Ana P. Fernandez, Julia Serrano, Pilar Calero, Hunter S. Futch, Rubén Corpas, Coral Sanfeliu, Gertrudis Perea, Alfonso Araque

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)569-580
Number of pages12
JournalGlia
Volume65
Issue number4
DOIs
StatePublished - Apr 1 2017

Bibliographical note

Funding Information:
Grant sponsor: Research Grant; Grant number: R01NS097312-01; Grant sponsor: NIH-NINDS; Grant numbers: R01NS097312-01 We thank W. Buño for helpful comments; B. Pro, S. Fernández and M. Palancar for technical assistance; Dr. J. Chen (UCSD, USA) for providing IP3R2−/− mice. Work supported by MINECO: SAF2015-65586 to RM; SAF2012-39852-C02-02 to CS; BFU2013-47265-R, BFU2016-75107-P, and RYC-2012-12014 to GP; CSD2010-00045 to CS, GP and AA; Cajal Blue Brain, Human Frontier Science Program and R01NS097312-01 to A.A.

Publisher Copyright:
© 2017 Wiley Periodicals, Inc.

Keywords

  • astrocytes
  • brain aging
  • gliotransmission
  • neuron–glia signaling
  • synaptic plasticity

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