How expensive is the astrocyte?

Barros, L. Felipe

doi:10.1177/0271678x221077343

Cited by 31 publications

(27 citation statements)

References 86 publications

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“…Interestingly, Lopez-Fabuel et al showed that decreased mitochondrial function and increased ROS production, promotes astrocyte survival while negatively influencing neuron viability [210]. This effect was further described by Weber and Barros, who discussed the “selfishness” of reactive astrocytes, observing that following injury or in response to disease, activated astrocytes will alter their metabolism and reduced their neuronal support functions to favour their own survival [211,212].…”

Section: Discussionmentioning

confidence: 99%

Micromotion derived fluid shear stress mediates peri-electrode gliosis through mechanosensitive ion channels

Trotier

Bagnoli

Walski

et al. 2023

Preprint

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Clinical applications for neural implant technologies are steadily advancing. Yet, despite clinical successes, neuroelectrode-based therapies require invasive neurosurgery and can subject local soft-tissues to micro-motion induced mechanical shear, leading to the development of peri-implant scaring. This reactive glial tissue creates a physical barrier to electrical signal propagation, leading to loss of device function. Although peri-electrode gliosis is a well described contributor to neuroelectrode failure, the mechanistic basis behind the initiation and progression of glial scarring remains poorly understood. Here, we develop an in silico model of electrode-induced shear stress to evaluate the evolution of the peri-electrode fluid-filled void, encompassing a solid and viscoelastic liquid/solid interface. This model was subsequently used to inform an in vitro parallel-plate flow model of micromotion mediated peri-electrode fluid shear stress. Ventral mesencephalic E14 rat embryonic in vitro cultures exposed to physiologically relevant fluid shear exhibited upregulation of gliosis-associated proteins and the overexpression of two mechanosensitive ion channel receptors, PIEZO1 and TRPA1, confirmed in vivo in a neural probe induced rat glial scar model. Finally, it was shown in vitro that chemical inhibition/activation of PIEZO1 could exacerbate or attenuate astrocyte reactivity as induced by fluid shear stress and that this was mitochondrial dependant. Together, our results suggests that mechanosensitive ion channels play a major role in the development of the neuroelectrode micromotion induced glial scar and that the modulation of PIEZO1 and TRPA1 through chemical agonist/antagonist may promote chronic electrode stability in vivo.

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Section: Discussionmentioning

confidence: 99%

Micromotion derived fluid shear stress mediates peri-electrode gliosis through mechanosensitive ion channels

Trotier

Bagnoli

Walski

et al. 2023

Preprint

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“…In addition, astrocytes express the constitutively open Kir4.1 channels, which act as routes of K + entry and efflux (MacAulay, 2020 ), and maintain a hyperpolarized membrane potential. Spatial buffering of astrocytic K + is achieved where K + influx via Kir4.1 channels is counteracted by electrotonic repulsion of K + from distant astrocytes in the interconnected syncytium (Barros, 2022 ; Orkand et al, 1966 ). The combination of these transport mechanisms is computed as the most energy efficient means of buffering interstitial K + (Barros, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

“…Spatial buffering of astrocytic K + is achieved where K + influx via Kir4.1 channels is counteracted by electrotonic repulsion of K + from distant astrocytes in the interconnected syncytium (Barros, 2022 ; Orkand et al, 1966 ). The combination of these transport mechanisms is computed as the most energy efficient means of buffering interstitial K + (Barros, 2022 ). Astrocytes occupy 30% of the volume of the MON and contain 70% of the mitochondria (Perge et al, 2009 ).…”

Section: Discussionmentioning

confidence: 99%

Resilience of compound action potential peaks to high‐frequency firing in the mouse optic nerve

Hopper

Beswick‐Jones

Brown

2023

Physiological Reports

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Action potential conduction in axons triggers trans‐membrane ion movements, where Na + enters and K + leaves axons, leading to disruptions in resting trans‐membrane ion gradients that must be restored for optimal axon conduction, an energy dependent process. The higher the stimulus frequency, the greater the ion movements and the resulting energy demand. In the mouse optic nerve (MON), the stimulus evoked compound action potential (CAP) displays a triple peaked profile, consistent with subpopulations of axons classified by size producing the distinct peaks. The three CAP peaks show differential sensitivity to high‐frequency firing, with the large axons, which contribute to the 1st peak, more resilient than the small axons, which produce the 3rd peak. Modeling studies predict frequency dependent intra‐axonal Na + accumulation at the nodes of Ranvier, sufficient to attenuate the triple peaked CAP. Short bursts of high‐frequency stimulus evoke transient elevations in interstitial K + ([K + ] o ), which peak at about 50 Hz. However, powerful astrocytic buffering limits the [K + ] o increase to levels insufficient to cause CAP attenuation. A post‐stimulus [K + ] o undershoot below baseline coincides with a transient increase in the amplitudes of all three CAP peaks. The volume specific scaling relating energy expenditure to increasing axon size dictates that large axons are more resilient to high‐frequency firing than small axons.

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“…In particular, we found that the levels of reduced c - and b -types cytochromes were lower in aged astrocytes reflecting the decreased amount of electrons in ETC which may limit the production of mitochondrial ATP and reactive oxygen species (ROS). Mitochondrial generation of ATP is critical for astrocytic homeostatic function, as ATP fuels Na + /K + ATPase responsible for K + buffering and maintenance of Na + gradients sustaining homeostatic transporters (Verkhratsky & Rose, 2020, Barros, 2022, Verkhratsky & Semyanov, 2022). ROS-signaling modulates brain metabolism and behavior (Vicente-Gutierrez et al ., 2019).…”

Section: Discussionmentioning

confidence: 99%

Aging impairs astrocytes in the human cerebral cortex

Popov¹,

Brazhe²,

Morozova³

et al. 2022

Preprint

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How aging affects cellular components of the human brain active milieu remains largely unknown. We analyzed astrocytes and neurons in the neocortical access tissue of younger (22 - 50 years) and older (51 - 72 years) adult patients who underwent glioma resection. Aging decreased the amount of reduced mitochondrial cytochromes in astrocytes but not neurons. The total amount of protein was decreased in astrocytes and increased in neurons. Aged astrocytes showed morphological dystrophy quantified by the decreased length of branches, decreased volume fraction of leaflets, and shrinkage of the anatomical domain. Dystrophy correlated with the loss of gap junction coupling between astrocytes and increased input resistance. Aging was accompanied by the upregulation of glial fibrillary acidic protein (GFAP) and downregulation of membrane-cytoskeleton linker Ezrin associated with leaflets. No significant changes in neuronal excitability or spontaneous inhibitory postsynaptic signaling were observed. Thus, brain aging is associated with the impaired morphological presence and mitochondrial malfunction of astrocytes, but not neurons.

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How expensive is the astrocyte?

Cited by 31 publications

References 86 publications

Micromotion derived fluid shear stress mediates peri-electrode gliosis through mechanosensitive ion channels

Micromotion derived fluid shear stress mediates peri-electrode gliosis through mechanosensitive ion channels

Resilience of compound action potential peaks to high‐frequency firing in the mouse optic nerve

Aging impairs astrocytes in the human cerebral cortex

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