Dataset Information

In Vivo Imaging of Secondary Neurodegeneration Associated With Phosphatidylserine Externalization Along Axotomized Axons.

ABSTRACT:

Purpose

Axonal degeneration in acute and chronic disorders is well-characterized, comprising retrograde (proximal) and Wallerian (distal) degeneration, but the mechanism of propagation remains less understood.

Methods

Laser injury with a diode-pumped solid-state 532 nm laser was used to axotomize retinal ganglion cell axons. We used confocal in vivo imaging to demonstrate that phosphatidylserine externalization is a biomarker of early axonal degeneration after selective intraretinal axotomy.

Results

Quantitative dynamic analysis revealed that the rate of axonal degeneration was fastest within 40 minutes, then decreased exponentially afterwards. Axonal degeneration was constrained within the same axotomized axonal bundles. Remarkably, axon degeneration arising from the site of injury induced a secondary degeneration of distal normal axons.

Conclusions

Axonal degeneration in vivo is a progressive process associated with phosphatidylserine externalization, which can propagate not only along the axon but to adjacent uninjured axons. This finding has implications for acute and chronic neurodegenerative disorders associated with axonal injury.

SUBMITTER: Yang F

PROVIDER: S-EPMC10866172 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Publications

In Vivo Imaging of Secondary Neurodegeneration Associated With Phosphatidylserine Externalization Along Axotomized Axons.

Yang Fan F Almasieh Mohammadali M Levin Leonard A LA

Investigative ophthalmology & visual science 20240201 2

<h4>Purpose</h4>Axonal degeneration in acute and chronic disorders is well-characterized, comprising retrograde (proximal) and Wallerian (distal) degeneration, but the mechanism of propagation remains less understood.<h4>Methods</h4>Laser injury with a diode-pumped solid-state 532 nm laser was used to axotomize retinal ganglion cell axons. We used confocal in vivo imaging to demonstrate that phosphatidylserine externalization is a biomarker of early axonal degeneration after selective intraretin ...[more]

PMID: 38345553

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Project description:ObjectivePhosphatidylserine exposure mediates platelet procoagulant function and regulates platelet life span. Apoptotic, necrotic, and integrin-mediated mechanisms have been implicated as intracellular determinants of platelet phosphatidylserine exposure. Here, we investigate (1) the role of mitochondrial events in platelet phosphatidylserine exposure initiated by these distinct stimuli and (2) the cellular interactions of the procoagulant platelet in vitro and in vivo.Approach and resultsKey mitochondrial events were examined, including cytochrome c release and inner mitochondrial membrane (IMM) disruption. In both ABT-737 (apoptotic) and agonist (necrotic)-treated platelets, phosphatidylserine externalization was temporally correlated with IMM disruption. Agonist stimulation resulted in rapid cyclophilin D-dependent IMM disruption that coincided with phosphatidylserine exposure. ABT-737 treatment caused rapid cytochrome c release, eventually followed by caspase-dependent IMM disruption that again closely coincided with phosphatidylserine exposure. A nonmitochondrial and integrin-mediated mechanism has been implicated in the formation of a novel phosphatidylserine-externalizing platelet subpopulation. Using image cytometry, this subpopulation is demonstrated to be the result of the interaction of an aggregatory platelet and a procoagulant platelet rather than indicative of a novel intracellular mechanism regulating platelet phosphatidylserine externalization. Using electron microscopy, similar interactions between aggregatory and procoagulant platelets are demonstrated in vitro and in vivo within a mesenteric vein hemostatic thrombus.ConclusionsPlatelet phosphatidylserine externalization is closely associated with the mitochondrial event of IMM disruption identifying a common pathway in phosphatidylserine-externalizing platelets. The limited interaction of procoagulant platelets and integrin-active aggregatory platelets identifies a potential mechanism for procoagulant platelet retention within the hemostatic thrombus.

Dataset Information

In Vivo Imaging of Secondary Neurodegeneration Associated With Phosphatidylserine Externalization Along Axotomized Axons.

Purpose

Methods

Results

Conclusions

Publications

In Vivo Imaging of Secondary Neurodegeneration Associated With Phosphatidylserine Externalization Along Axotomized Axons.

Similar Datasets

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