Spontaneous astrocytic Ca2+ activity abounds in electrically suppressed ischemic penumbra of aged mice
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Spontaneous astrocytic Ca2+ activity abounds in electrically suppressed ischemic penumbra of aged mice. / Fordsmann, Jonas Christoffer; Murmu, Reena Prity; Cai, Changsi; Brazhe, Alexey; Thomsen, Kirsten Joan; Zambach, Stefan Andreas; Lønstrup, Micael; Lind, Barbara Lykke; Lauritzen, Martin.
In: Glia, Vol. 67, No. 1, 2019, p. 37-52.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Spontaneous astrocytic Ca2+ activity abounds in electrically suppressed ischemic penumbra of aged mice
AU - Fordsmann, Jonas Christoffer
AU - Murmu, Reena Prity
AU - Cai, Changsi
AU - Brazhe, Alexey
AU - Thomsen, Kirsten Joan
AU - Zambach, Stefan Andreas
AU - Lønstrup, Micael
AU - Lind, Barbara Lykke
AU - Lauritzen, Martin
N1 - © 2018 Wiley Periodicals, Inc.
PY - 2019
Y1 - 2019
N2 - Experimental focal cortical ischemic lesions consist of an ischemic core and a potentially salvageable peri-ischemic region, the ischemic penumbra. The activity of neurons and astrocytes is assumed to be suppressed in the penumbra because the electrical function is interrupted, but this is incompletely elucidated. Most experimental stroke studies used young adult animals, whereas stroke is prevalent in the elderly population. Using two-photon imaging in vivo, we here demonstrate extensive but electrically silent, spontaneous Ca2+ activity in neurons and astrocytes in the ischemic penumbra of 18- to 24-month-old mice 2-4 hr after middle cerebral artery occlusion. In comparison, stroke reduced spontaneous Ca2+ activity in neurons and astrocytes in adult mice (3-4 months of age). In aged mice, stroke increased astrocytic spontaneous Ca2+ activity considerably while neuronal spontaneous Ca2+ activity was unchanged. Blockade of action potentials and of purinergic receptors strongly reduced spontaneous Ca2+ activity in both neurons and astrocytes in the penumbra of old stroke mice. This indicates that stroke had a direct influence on mechanisms in presynaptic terminals and on purinergic signaling. Thus, highly dynamic variations in spontaneous Ca2+ activity characterize the electrically compromised penumbra, with remarkable differences between adult and old mice. The data are consistent with the notion that aged neurons and astrocytes take on a different phenotype than young mice. The increased activity of the aged astrocyte phenotype may be harmful to neurons. We suggest that the abundant spontaneous Ca2+ activity in astrocytes in the ischemic penumbra of old mice may be a novel target for neuroprotection strategies. A video abstract of this article can be found at https://youtu.be/AKlwKFsz1qE.
AB - Experimental focal cortical ischemic lesions consist of an ischemic core and a potentially salvageable peri-ischemic region, the ischemic penumbra. The activity of neurons and astrocytes is assumed to be suppressed in the penumbra because the electrical function is interrupted, but this is incompletely elucidated. Most experimental stroke studies used young adult animals, whereas stroke is prevalent in the elderly population. Using two-photon imaging in vivo, we here demonstrate extensive but electrically silent, spontaneous Ca2+ activity in neurons and astrocytes in the ischemic penumbra of 18- to 24-month-old mice 2-4 hr after middle cerebral artery occlusion. In comparison, stroke reduced spontaneous Ca2+ activity in neurons and astrocytes in adult mice (3-4 months of age). In aged mice, stroke increased astrocytic spontaneous Ca2+ activity considerably while neuronal spontaneous Ca2+ activity was unchanged. Blockade of action potentials and of purinergic receptors strongly reduced spontaneous Ca2+ activity in both neurons and astrocytes in the penumbra of old stroke mice. This indicates that stroke had a direct influence on mechanisms in presynaptic terminals and on purinergic signaling. Thus, highly dynamic variations in spontaneous Ca2+ activity characterize the electrically compromised penumbra, with remarkable differences between adult and old mice. The data are consistent with the notion that aged neurons and astrocytes take on a different phenotype than young mice. The increased activity of the aged astrocyte phenotype may be harmful to neurons. We suggest that the abundant spontaneous Ca2+ activity in astrocytes in the ischemic penumbra of old mice may be a novel target for neuroprotection strategies. A video abstract of this article can be found at https://youtu.be/AKlwKFsz1qE.
U2 - 10.1002/glia.23506
DO - 10.1002/glia.23506
M3 - Journal article
C2 - 30427548
VL - 67
SP - 37
EP - 52
JO - GLIA
JF - GLIA
SN - 0894-1491
IS - 1
ER -
ID: 209737676