Impaired astrocytic Ca2+ signalling in awake Alzheimer's disease transgenic mice

Abjorsbraten, K. S.; Skaaraas, G. H. E. S.; Cunen, C.; Bjornstad, D. M.; Binder, K. M. G.; Jensen, V.; Nilsson, L. N.; Rao, S. B.; Tang, W.; Hermansen, G. H.; Nagelhus, E. A.; Ottersen, O. P.; Torp, R.; Enger, R.

doi:10.1101/2021.11.21.469461

bioRxiv · 10.1101/2021.11.21.469461

Impaired astrocytic Ca2+ signalling in awake Alzheimer's disease transgenic mice

Abjorsbraten, K. S.·Skaaraas, G. H. E. S.·Cunen, C.·Bjornstad, D. M.·Binder, K. M. G.·Jensen, V.·Nilsson, L. N.·Rao, S. B.·Tang, W.·Hermansen, G. H.·Nagelhus, E. A.·Ottersen, O. P.·Torp, R.·Enger, R.

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Abstract

Increased astrocytic Ca2+ signaling related to amyloid plaques has been shown in Alzheimers disease mouse models, but to date no reports have characterized behaviorally induced astrocytic Ca2+ signalling in such mice without the confounding effects of anesthesia. Here, we employ an event-based algorithm to assess astrocytic Ca2+ signals in the neocortex of awake-behaving tg-ArcSwe mice and non-transgenic wildtype littermates while monitoring pupil responses and behavior. We demonstrate an attenuated astrocytic Ca2+ response to locomotion and an uncoupling of pupil responses and astrocytic Ca2+ signalling in 15-months old plaque-bearing mice. This points to a potential decoupling of neuromodulatory activation and astrocytic Ca2+ activity, which may account for some of the cognitive dysfunctions observed in Alzheimers disease.

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Abjorsbraten, K. S., Skaaraas, G. H. E. S., Cunen, C., Bjornstad, D. M., Binder, K. M. G., Jensen, V., Nilsson, L. N., Rao, S. B., Tang, W., Hermansen, G. H., Nagelhus, E. A., Ottersen, O. P., Torp, R., Enger, R.. 2021-11-24. Impaired astrocytic Ca2+ signalling in awake Alzheimer's disease transgenic mice. https://doi.org/10.1101/2021.11.21.469461

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