3D Modelling of a Spatially Resolved Energy Metabolism in Physiological Astrocytic Morphology

Scientific Conference (2022)

Astrocytes, the most abundant cell in the central nervous system, have a star-shaped morphology and play a central role in brain homeostasis as metabolic mediators between neurons and blood vessels ... [more ▼]

Astrocytes, the most abundant cell in the central nervous system, have a star-shaped morphology and play a central role in brain homeostasis as metabolic mediators between neurons and blood vessels. Recent evidence put astrocytes therefore in the focus of neurodegeneration (ND), since in case of metabolic dysfunctions as e.g. observed in Alzheimer’s disease or Parkinson’s disease, they cannot provide neurons with sufficient amount of nutrients. Furthermore, progression of ND is often accompanied by changes in astrocytic morphology further indicating the essential role of astrocytes in the brain. Despite its importance, the complex astrocytic morphology is often neglected in modelling of metabolic reactions [1]. In this study, we propose a computational model that describes cellular metabolism through a reaction-diffusion system including two fundamental pieces of information: the intracellular spatial arrangement of the reaction sites and the real, complex geometries by using the previously developed method CutFEM([2][3]). Our findings show how intracellular spatial organisation and diffusion limitation as well as the physio- logical cell shape must be taken into account to go towards biological models that are closer to reality. In particular, the spatial distribution of mitochondria notably impacts the cellular ATP : ADP ratio, which is an indicator of the energetic state of the cell. Finally, we solve our system in a 3D human astrocytic morphology and study the different spatial arrangements of the reaction sites simulating physiological and dysfunctional behaviour. In this regard, we believe, that the proposed model is a useful instrument to gain insights into the role astrocytes play in neurodegeneration. [less ▲]

PRAQA: Protein Relative Abundance Quantification Algorithm for 3D Fluorescent Images.

in BIOIMAGING (2021)

A Specialized Method to Resolve Fine 3D Features of Astrocytes in Nonhuman Primate (Marmoset, Callithrix jacchus) and Human Fixed Brain Samples.

in Methods in Molecular Biology (2019), 1938

Astrocytes are among the most numerous cells in the brain and fulfill diverse functions in homeostasis and regulation of neuronal activity. Astrocytes also dramatically change their properties in response ... [more ▼]

Astrocytes are among the most numerous cells in the brain and fulfill diverse functions in homeostasis and regulation of neuronal activity. Astrocytes also dramatically change their properties in response to brain injury or disease, a process called reactive gliosis. Precisely how astrocytes contribute to healthy brain function and play differential roles in brain pathology and regeneration remain important areas of investigation. To better understand the properties of astrocytes, more sophisticated approaches for probing their rich and complex anatomical and molecular features are needed to fully determine their contribution to brain physiology. Here we present an efficient and straightforward immunolabeling protocol to obtain high-resolution fluorescence-based images from fixed nonhuman primate (common marmoset Callithrix jacchus) and human brain samples. Importantly, the protocol is useful for obtaining images from samples that have been stored in fixative solutions (such as formalin) for years. This approach is especially useful for three-dimensional, multichannel confocal microscopy and can be optimized for super-resolution techniques such as stimulated emission depletion (STED) microscopy. We also present a strategy for using specific combinations of markers to define the phenotypic variations and cellular/subcellular properties of astrocytes to better predict the function of these cells on their surrounding brain microenvironment. [less ▲]