Neuron-astrocyte signaling is preserved in the aging brain.
Glia. 2017-01-28; 65(4): 569-580
DOI: 10.1002/glia.23112
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Gómez-Gonzalo M(1), Martin-Fernandez M(2), Martínez-Murillo R(1), Mederos S(1), Hernández-Vivanco A(1), Jamison S(2), Fernandez AP(1), Serrano J(1), Calero P(1), Futch HS(3), Corpas R(4), Sanfeliu C(4), Perea G(1), Araque A(2).
Author information:
(1)Instituto Cajal, CSIC, Madrid, 28002, Spain.
(2)Department of Neuroscience, University of Minnesota, Minneapolis, 55455.
(3)College of Medicine, University of Florida, Gainesville, Florida, 32610-0261.
(4)Aging and Neurodegeneration Unit, Biomedical Research Institute of Barcelona
(IIBB), CSIC and IDIBAPS, Barcelona, 08036, Spain.
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 IP3 R2 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.
© 2017 Wiley Periodicals, Inc.
Conflict of interest statement: The authors have no conflict of interest to
declare.