Laura Bojarskaite

• Bojarskaite, Laura; Nafari, Sahar; Ravnanger, Anne Katrine; Frey, Mina Martine; Skauli, Nadia & Åbjørsbråten, Knut Sindre [Show all 13 contributors for this article] (2024). Role of aquaporin-4 polarization in extracellular solute clearance. Fluids and Barriers of the CNS. 21(1). doi: 10.1186/s12987-024-00527-7. Full text in Research Archive Show summary

  Waste from the brain has been shown to be cleared via the perivascular spaces through the so-called glymphatic system. According to this model the cerebrospinal fluid (CSF) enters the brain in perivascular spaces of arteries, crosses the astrocyte endfoot layer, flows through the parenchyma collecting waste that is subsequently drained along veins. Glymphatic clearance is dependent on astrocytic aquaporin-4 (AQP4) water channels that are highly enriched in the endfeet. Even though the polarized expression of AQP4 in endfeet is thought to be of crucial importance for glymphatic CSF influx, its role in extracellular solute clearance has only been evaluated using non-quantitative fluorescence measurements. Here we have quantitatively evaluated clearance of intrastriatally infused small and large radioactively labeled solutes in mice lacking AQP4 (Aqp4–/–) or lacking the endfoot pool of AQP4 (Snta1–/–). We confirm that Aqp4–/– mice show reduced clearance of both small and large extracellular solutes. Moreover, we find that the Snta1–/– mice have reduced clearance only for the 500 kDa [3H]dextran, but not 0.18 kDa [3H]mannitol suggesting that polarization of AQP4 to the endfeet is primarily important for clearance of large, but not small molecules. Lastly, we observed that clearance of 500 kDa [3H]dextran increased with age in adult mice. Based on our quantitative measurements, we confirm that presence of AQP4 is important for clearance of extracellular solutes, while the perivascular AQP4 localization seems to have a greater impact on clearance of large versus small molecules.

• Bojarskaite, Laura; Vallet, Alexandra Honorine Emilie; Bjørnstad, Daniel Marelius; Binder, Kristin Maria Gullestad; Cunen, Celine & Heuser, Kjell [Show all 9 contributors for this article] (2023). Sleep cycle-dependent vascular dynamics in male mice and the predicted effects on perivascular cerebrospinal fluid flow and solute transport. Nature Communications. 14. doi: 10.1038/s41467-023-36643-5. Full text in Research Archive Show summary

  Perivascular spaces are important highways for fluid and solute transport in the brain enabling efficient waste clearance during sleep. However, the underlying mechanisms augmenting perivascular flow in sleep are unknown. Using two-photon imaging of naturally sleeping male mice we demonstrate sleep cycle-dependent vascular dynamics of pial arteries and penetrating arterioles: slow, large-amplitude oscillations in NREM sleep, a vasodilation in REM sleep, and a vasoconstriction upon awakening at the end of a sleep cycle and microarousals in NREM and intermediate sleep. These vascular dynamics are mirrored by changes in the size of the perivascular spaces of the penetrating arterioles: slow fluctuations in NREM sleep, reduction in REM sleep and an enlargement upon awakening after REM sleep and during microarousals in NREM and intermediate sleep. By biomechanical modeling we demonstrate that these sleep cycle-dependent perivascular dynamics likely enhance fluid flow and solute transport in perivascular spaces to levels comparable to cardiac pulsation-driven oscillations.

• Åbjørsbråten, Knut Sindre; Skaaraas, Gry Helen Enger Syverstad; Cunen, Celine Marie Løken; Bjørnstad, Daniel Marelius; Binder, Kristin Maria Gullestad & Bojarskaite, Laura [Show all 15 contributors for this article] (2022). Impaired astrocytic Ca2+ signaling in awake-behaving Alzheimer’s disease transgenic mice. eLIFE. doi: 10.7554/eLife.75055. Full text in Research Archive Show summary

  Increased astrocytic Ca2+ signaling has been shown in Alzheimer’s disease mouse models, but to date no reports have characterized behaviorally induced astrocytic Ca2+ signaling in such mice. 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+ signaling in 15-month-old plaque-bearing mice. Using the genetically encoded fluorescent norepinephrine sensor GRABNE, we demonstrate a reduced norepinephrine signaling during spontaneous running and startle responses in the transgenic mice, providing a possible mechanistic underpinning of the observed reduced astrocytic Ca2+ responses. Our data points to a dysfunction in the norepinephrine–astrocyte Ca2+ activity axis, which may account for some of the cognitive deficits observed in Alzheimer’s disease.

• Bjørnstad, Daniel Marelius; Åbjørsbråten, Knut Sindre; Hennestad, Eivind; Cunen, Celine; Hermansen, Gudmund Horn & Bojarskaite, Laura [Show all 9 contributors for this article] (2021). Begonia - a two-photon imaging analysis pipeline for astrocytic Ca2+ signals. Frontiers in Cellular Neuroscience. 15. doi: 10.3389/fncel.2021.681066. Full text in Research Archive Show summary

  Imaging the intact brain of awake behaving mice without the dampening effects of anesthesia, has revealed an exceedingly rich repertoire of astrocytic Ca 2+ signals. Analyzing and interpreting such complex signals pose many challenges. Traditional analyses of fluorescent changes typically rely on manually outlined static region-of-interests, but such analyses fail to capture the intricate spatiotemporal patterns of astrocytic Ca 2+ dynamics. Moreover, all astrocytic Ca 2+ imaging data obtained from awake behaving mice need to be interpreted in light of the complex behavioral patterns of the animal. Hence processing multimodal data, including animal behavior metrics, stimulation timings, and electrophysiological signals is needed to interpret astrocytic Ca 2+ signals. Managing and incorporating these data types into a coherent analysis pipeline is challenging and time-consuming, especially if research protocols change or new data types are added. Here, we introduce Begonia, a MATLAB-based data management and analysis toolbox tailored for the analyses of astrocytic Ca 2+ signals in conjunction with behavioral data. The analysis suite includes an automatic, event-based algorithm with few input parameters that can capture a high level of spatiotemporal complexity of astrocytic Ca 2+ signals. The toolbox enables the experimentalist to quantify astrocytic Ca 2+ signals in a precise and unbiased way and combine them with other types of time series data.

• Bojarskaite, Laura; Bjørnstad, Daniel Marelius; Pettersen, Klas Henning; Cunen, Celine; Hermansen, Gudmund Horn & Åbjørsbråten, Knut Sindre [Show all 12 contributors for this article] (2020). Astrocytic Ca2+ signaling is reduced during sleep and is involved in the regulation of slow wave sleep. Nature Communications. 11. doi: 10.1038/s41467-020-17062-2. Full text in Research Archive Show summary

  Astrocytic Ca2+ signaling has been intensively studied in health and disease but has not been quantified during natural sleep. Here, we employ an activity-based algorithm to assess astrocytic Ca2+ signals in the neocortex of awake and naturally sleeping mice while monitoring neuronal Ca2+ activity, brain rhythms and behavior. We show that astrocytic Ca2+ signals exhibit distinct features across the sleep-wake cycle and are reduced during sleep compared to wakefulness. Moreover, an increase in astrocytic Ca2+ signaling precedes transitions from slow wave sleep to wakefulness, with a peak upon awakening exceeding the levels during whisking and locomotion. Finally, genetic ablation of an important astrocytic Ca2+ signaling pathway impairs slow wave sleep and results in an increased number of microarousals, abnormal brain rhythms, and an increased frequency of slow wave sleep state transitions and sleep spindles. Our findings demonstrate an essential role for astrocytic Ca2+ signaling in regulating slow wave sleep.

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• Enger, Rune & Bojarskaite, Laura (2021). Hjernens vaktmestere - nattlig hjernevask og søvnregulering. SØVN. ISSN 1891-5493. Full text in Research Archive
• Bojarskaite, Laura; Enger, Rune; Hu, Hua & Boccara, Charlotte (2020). Hvorfor sover vi? Full text in Research Archive
• Boccara, Charlotte N; Hu, Hua; Enger, Rune & Bojarskaite, Laura (2020). Hvorfor sover vi? Full text in Research Archive

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