Ottersen, O. P. | bioRxiv Science

bioRxiv2021

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

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.

neuroscience↗

bioRxiv2018

Low oxygen post conditioning improves stroke-induced cognitive impairment

Post-stroke cognitive impairment has proven to be notoriously difficult to treat. In the current study, we sought to both better understand cellular changes that underpin cognitive deficits and to consider the potential restorative benefits of low oxygen post conditioning (LOPC). We were motivated to use LOPC as an intervention as it is one of the few experimental interventions previously shown to improve cognitive function post-stroke. Experimental stroke was induced by photothrombotic occlusion in adult male C57BL/6 mice. Mice were randomly assigned to either a normal atmospheric air exposure or low oxygen (11% O2) exposure groups three days post-occlusion. On day 17 post-stroke, mice were euthanized for histology or biochemical analyses. Stroked mice exposed to LOPC was associated with marked reductions in amyloid-beta both in its absolute level and in the extent of its oligomerization. Exposure to LOPC post-stroke also improved cellular deficits induced by stroke including an increase in vessel density, a reduction in vascular leakage, and restoration of AQP4 polarisation. Critically, stroked mice exposed to LOPC exhibited robust improvements in cognitive function post-stroke, assessed using a touchscreen based paired-associate learning task. These findings provide compelling pre-clinical evidence of the potential clinical utility of LOPC for enhancing recovery post-stroke.

neuroscience↗