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Visualizing astroglial motility in a mouse model of Alzheimer's disease using live-cell imaging [Interview with Dr. Lusine Danielyan]

Time-lapse imaging and analysis of cell motility in vitro can provide critical temporal and spatial information, allowing to develop a better understanding of this complex cellular process. A recent study by Drews et al. (2021) conducted under the supervision of Asst. Prof. Lusine Danielyan, Prof. Matthias Schwab, and Prof. Christoph H. Gleiter, focuses on examining broad neuroprotective features of angiotensin receptor blocker (ARB), losartan. Losartan was administered systemically to the amyloid precursor protein / presenilin 1 (APP / PS1) mouse model of Alzheimer’s disease and the effects of this treatment on memory, cell motility, and neurogenesis were investigated. The motility of Aβ-affected astrocytes was tracked by the CytoSMART Lux3 FL fluorescence live-cell imager. The members of the CytoSMART team – Mr. Tom de Vries and Dr. Inge Thijssen-van Loosdregt – provided assistance with methodology and cell motility data analysis.

To learn more about the use of the CytoSMART devices in life sciences, we asked Dr. Lusine Danielyan a few questions about her experience with using the Lux3 FL for cellular imaging. Dr. Lusine Danielyan is a board certified Pharmacologist, Assistant Professor and Head of the Laboratory of Cellular/Molecular Pharmacology at the University of Tübingen, Germany. Dr. Danielyan’s current research is centered around investigating the neuroprotective effects of pharmaceutical agents and therapeutic cells in neurological disorders, such as Alzheimer’s disease, Parkinson’s disease, and stroke.

Q: Dr. Danielyan, could you tell us a little more about the research that is performed in your group?

Dr. Danielyan: Our research is focused on neuroprotection provided by different drugs and cell therapeutics in treatment of neurodegenerative disorders. Our recent findings have shown that multifaceted protection provided by stem cell therapies relies on their capacity of targeted migration to the disease loci. In this context exploration of the key factors influencing the cell migration is of great importance for both, cell based and neurogenesis-enhancing therapies.

Q: You have recently published your latest research on the effects of losartan on memory, neurogenesis, and cell motility in Alzheimer’s mice. In this paper, you have used the CytoSMART Lux3 FL and received some help from the CytoSMART team. Could you tell us about the most important findings of this study?

Dr. Danielyan: Our study demonstrated a remarkable efficacy of an antihypertensive drug, losartan, to improve memory, cholinergic activity, and neurogenesis as well as to decrease neuroinflammation in a mouse model of Alzheimer’s disease. Moreover, losartan was capable of increasing the motility and migration of astrocytes (Figure 1). Future investigations are required to explore whether this migration-inducing effect will help to improve the protective features of astrocytes and potentially microglia in neurodegenerative disorders.

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b)

Figure 1. Astroglial primary cultures (APC) derived from triple-transgenic mouse model of Alzheimer’s disease (3×Tg-AD) were tracked without (a) and with the addition of 1 μM losartan (b) for 24 hours. The images were taken every 15 minutes by the CytoSMART Lux3 FL. The tracking analysis was performed using ImageJ plug-in “TrackMate” as described in the methods section of the paper.

Q: Could you tell us how the Lux3 FL has contributed to this study?

Dr. Danielyan: Lux3 FL provided a simple and efficacious tool of live-cell imaging and tracking of cell migration. Having an experience in working with other cell imaging systems in the past, I was surprised to discover that such simple microscope system would show non-inferiority to other systems in tracking cell migration, as long as the experimental design does not require an advanced analysis of high resolution and magnification of living cells.

Q: How was your experience working with the CytoSMART team?

Dr. Danielyan: The CytoSMART team provided excellent technical and methodological support in data analysis and evaluation of cell migration, which helped us to prove the influence of losartan on the motility and migratory capacity of astroglial cells. They have invested a great deal of time in analyzing data and training my team in cell tracking analysis, which not only helped us in accomplishing the project reported in this paper, but also will speed up the data analysis process in our ongoing and future investigations.

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