Parametric exploration of cellular swelling in a computational model of cortical spreading depression

Genocchi, Barbara; Cunha, André B.; Jain, Soumil; Hyttinen, Jari; Lenk, Kerstin; Ellingsrud, Ada J.

doi:10.1109/embc44109.2020.9175306

Cited by 4 publications

(4 citation statements)

References 18 publications

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“…A recent study by Genocchi et al (2020) used a computational model of cortical spreading depression to explore how different parameters, including changes in AQP4 channel expression in astrocytes, neuron/astrocyte ratio and activity of Na + /K + -ATPase or chloride channels affect the swelling of neurons and astrocytes. Their results show that changes in each of these parameters may shift the proportion between neuronal and astrocytic swelling (Genocchi et al, 2020). Our results of astrocytic gene profiling undoubtably showed significant differences in the expression of some of the abovementioned genes.…”

Section: Changes In the Morphology Of Astrocytes And Their Effect On Extracellular Space Diffusion Parametersmentioning

confidence: 99%

“…This discrepancy is highly probable due to the shift in the proportion of swelling of cells that can regulate their volume (astrocytes) and cells which are not capable of regulation (neurons and possibly other types) (Risher et al, 2009). Genocchi et al (2020) calculated that this shift can be induced by alterations in expression of specific channels involved in volume and ionic homeostasis. In 12M 3xTg-AD mice, the recovery of α following hypo-osmotic stress was significantly smaller compared to age-matched controls.…”

Section: Single Astrocyte Volume Changes and Their Relationship To Expression Levels Of Channels And Transportersmentioning

confidence: 99%

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Compromised Astrocyte Swelling/Volume Regulation in the Hippocampus of the Triple Transgenic Mouse Model of Alzheimer’s Disease

Tureckova

Kamenicka

Koleničová

et al. 2022

Front. Aging Neurosci.

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In this study, we aimed to disclose the impact of amyloid-β toxicity and tau pathology on astrocyte swelling, their volume recovery and extracellular space (ECS) diffusion parameters, namely volume fraction (α) and tortuosity (λ), in a triple transgenic mouse model of Alzheimer’s disease (3xTg-AD). Astrocyte volume changes, which reflect astrocyte ability to take up ions/neurotransmitters, were quantified during and after exposure to hypo-osmotic stress, or hyperkalemia in acute hippocampal slices, and were correlated with alterations in ECS diffusion parameters. Astrocyte volume and ECS diffusion parameters were monitored during physiological aging (controls) and during AD progression in 3-, 9-, 12- and 18-month-old mice. In the hippocampus of controls α gradually declined with age, while it remained unaffected in 3xTg-AD mice during the entire time course. Moreover, age-related increases in λ occurred much earlier in 3xTg-AD animals than in controls. In 3xTg-AD mice changes in α induced by hypo-osmotic stress or hyperkalemia were comparable to those observed in controls, however, AD progression affected α recovery following exposure to both. Compared to controls, a smaller astrocyte swelling was detected in 3xTg-AD mice only during hyperkalemia. Since we observed a large variance in astrocyte swelling/volume regulation, we divided them into high- (HRA) and low-responding astrocytes (LRA). In response to hyperkalemia, the incidence of LRA was higher in 3xTg-AD mice than in controls, which may also reflect compromised K+ and neurotransmitter uptake. Furthermore, we performed single-cell RT-qPCR to identify possible age-related alterations in astrocytic gene expression profiles. Already in 3-month-old 3xTg-AD mice, we detected a downregulation of genes affecting the ion/neurotransmitter uptake and cell volume regulation, namely genes of glutamate transporters, α2β2 subunit of Na+/K+-ATPase, connexin 30 or Kir4.1 channel. In conclusion, the aged hippocampus of 3xTg-AD mice displays an enlarged ECS volume fraction and an increased number of obstacles, which emerge earlier than in physiological aging. Both these changes may strongly affect intercellular communication and influence astrocyte ionic/neurotransmitter uptake, which becomes impaired during aging and this phenomenon is manifested earlier in 3xTg-AD mice. The increased incidence of astrocytes with limited ability to take up ions/neurotransmitters may further add to a cytotoxic environment.

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Section: Changes In the Morphology Of Astrocytes And Their Effect On Extracellular Space Diffusion Parametersmentioning

confidence: 99%

Section: Single Astrocyte Volume Changes and Their Relationship To Expression Levels Of Channels And Transportersmentioning

confidence: 99%

Compromised Astrocyte Swelling/Volume Regulation in the Hippocampus of the Triple Transgenic Mouse Model of Alzheimer’s Disease

Tureckova

Kamenicka

Koleničová

et al. 2022

Front. Aging Neurosci.

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“…The reader will benefit from reading different approaches from ours in the work of several laboratories, including those of Mori, 55,354,[394][395][396][397][398][399][400][401][402][403][404] Ellingsrud, [405][406][407][408][409][410] Sacco, 411 and the many groups interested in glymphatics, sampled elsewhere. [47][48][49][50][51][52][53][54][55][56][57] While few if any of these papers deal with potassium accumulation in tridomain systems, no doubt their methods could be usefully applied to those issues.…”

Section: Ion Transportmentioning

confidence: 99%

Structural analysis of fluid flow in complex biological systems

Eisenberg

2023

MAIO

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Biology is about structure. Structures within structures. Organs within animals, tissues within organs, cells within tissues, and molecules, often proteins within cells. The structures are so complex that they can only be described by numbers. No numbers are of more importance than those that describe proteins. The numbers that describe coordinates of its atoms, often determined by Patterson functions (which are inverse Fourier Transforms of intensities) of crystal diffraction. Without these numbers, structural biology would hardly exist. Without numbers, engineering would not exist. Numbers are surely needed by the engineers who produce the x-rays diffracting from atoms of protein crystals. Devices of engineering have function. They are built to implement equations. Engineering devices use structures to implement equations, when power is supplied at the right places, that produces appropriate flows. Flows are the essence of life. Equilibrium means death in most living systems. Flows in biological structures are hard to analyze because we do not know input output equations in advance. Sometimes we do not know the function of the structures. Flows, forces, and structures of life (like those of engineering) are related by field equations of conservation laws, partial differential equations, constrained by location and properties of structures. Constraints are boundary conditions located on the complicated domain of biological structure. The hierarchy of structures allows a handful of atoms (in proteins and nucleic acids) to control macroscopic function. Dealing with this complexity is simplified if one systematically analyzes structure using the most general field theory known, electricity described by the Maxwell equations, without significant known error. Currents are involved because flows of biology usually involve migration of charges, convection of water and solutes, diffusion of ions that form the plasma of life, and their interactions. Interactions can dominate function. Here I show how a few complex structures can be understood in engineering detail. This approach may be useful in dealing with biological and medical issues in many other cases. In one limited case—the clearance of a toxic waste (potassium ions) from the optic nerve—this approach seems to have succeeded.

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“…The reader will benefit from reading different approaches from ours in the work of several laboratories, including those of Mori (55,354,(394)(395)(396)(397)(398)(399)(400)(401)(402)(403)(404), Ellingsrud (405)(406)(407)(408)(409)(410), Sacco (411) and the many groups interested in glymphatics, sampled in (47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57). While few if any of these papers deal with potassium accumulation in tridomain systems, no doubt their methods could be usefully applied to those issues.…”

Section: Ion Transport We Define the Regionsmentioning

confidence: 99%

Structural Analysis of Fluid Flow in Complex Biological Systems

Eisenberg¹

2022

Preprint

View full text Add to dashboard Cite

Biology is about structure. Structures within structures. Organs within animals, tissues within organs, cells within tissues, and molecules, often proteins within cells. The structures are so complex that they can only be described by numbers. No numbers are of more importance than those that describe proteins. The numbers that describe coordinates of its atoms, often determined by Patterson functions (which are inverse Fourier Transforms of intensities) of crystal diffraction. Without these numbers, structural biology would hardly exist. Without numbers, engineering would not exist. Numbers are surely needed by the engineers who produce the x-rays diffracting from atoms of protein crystals. Devices of engineering have function. They are built to implement equations. Engineering devices use structures to implement equations, when power is supplied at the right places, that produces appropriate flows. Flows are the essence of life. Equilibrium means death in most living systems. Flows in biological structures are hard to analyze because we do not know input output equations in advance. Sometimes we do not know their function. Flows, forces, and structures of life (like those of engineering) are related by field equations of conservation laws, partial differential equations, constrained by location and properties of structures. Constraints are boundary conditions located on the complicated domain of biological structure. Dealing with this complexity is simplified if one systematically analyzes structure using the most general field theory known, electricity described by the Maxwell equations, without significant known error. Currents are involved because flows of biology usually involve migration of charges, convection of water and solutes, diffusion of ions that form the plasma of life, and their interactions. Interactions can dominate function. Here I show how a few complex structures can be understood in engineering detail. This approach may be useful in dealing with biological and medical issues in many other cases. In one limited case—the clearance of a toxic waste (potassium ions) from the optic nerve—this approach seems to have succeeded.

show abstract

Parametric exploration of cellular swelling in a computational model of cortical spreading depression

Cited by 4 publications

References 18 publications

Compromised Astrocyte Swelling/Volume Regulation in the Hippocampus of the Triple Transgenic Mouse Model of Alzheimer’s Disease

Compromised Astrocyte Swelling/Volume Regulation in the Hippocampus of the Triple Transgenic Mouse Model of Alzheimer’s Disease

Structural analysis of fluid flow in complex biological systems

Structural Analysis of Fluid Flow in Complex Biological Systems

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