Nystatin Regulates Axonal Extension and Regeneration by Modifying the Levels of Nitric Oxide

doi:10.3389/fnmol.2020.00056

Paper

Nystatin Regulates Axonal Extension and Regeneration by Modifying the Levels of Nitric Oxide

Published Apr 3, 2020 · Cristina Roselló-Busquets, Marc Hernaiz-Llorens, E. Soriano

Frontiers in Molecular Neuroscience

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5

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Abstract

Nystatin is a pharmacological agent commonly used for the treatment of oral, mucosal and cutaneous fungal infections. Nystatin has also been extensively applied to study the cellular function of cholesterol-enriched structures because of its ability to bind and extract cholesterol from mammalian membranes. In neurons, cholesterol level is tightly regulated, being essential for synapse and dendrite formation, and axonal guidance. However, the action of Nystatin on axon regeneration has been poorly evaluated. Here, we examine the effect of Nystatin on primary cultures of hippocampal neurons, showing how acute dose (minutes) of Nystatin increases the area of growth cones, and chronic treatment (days) enhances axon length, axon branching, and axon regeneration post-axotomy. We describe two alternative signaling pathways responsible for the observed effects and activated at different concentrations of Nystatin. At elevated concentrations, Nystatin promotes growth cone expansion through phosphorylation of Akt; whereas, at low concentrations, Nystatin enhances axon length and regrowth by increasing nitric oxide levels. Together, our findings indicate new signaling pathways of Nystatin and propose this compound as a novel regulator of axon regeneration.

In Vitro Study

Study Snapshot

Nystatin enhances axon regeneration in hippocampal neurons by promoting growth cone expansion through Akt phosphorylation and enhancing nitric oxide levels.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Nystatin Regulates Axonal Extension and Regeneration by Modifying the Levels of Nitric Oxide

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References

The Struggle to Make CNS Axons Regenerate: Why Has It Been so Difficult?

CNS axon regeneration is hindered by multiple factors, and successful regeneration requires ensuring the right molecules are expressed and transported to the damaged axon tip in the neuron.

Cholesterol Depletion Regulates Axonal Growth and Enhances Central and Peripheral Nerve Regeneration

Cholesterol depletion promotes axonal growth in developing neurons and enhances axonal regeneration in vitro and in vivo, benefiting both central and peripheral nervous systems.

ALS-Linked SOD1 Mutants Enhance Neurite Outgrowth and Branching in Adult Motor Neurons

ALS-linked SOD1 mutants enhance the regenerative capability of adult motor neurons, potentially leading to new therapeutic strategies.

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Manipulating intracellular mechanisms can potentially lead to a regenerative response after central nervous system injury.

Cytoskeleton dynamics in axon regeneration

Modulating cytoskeleton dynamics can promote axon regeneration and potentially serve as a basis for regenerative therapy after spinal cord injury.

Citations

Effect of nystatin on invasion of Serratia grimesii and Serratia proteamaculans bacteria into epithelial cells

Nystatin reduces the internalization of Serratia grimesii and S. proteamaculans bacteria into epithelial cells, potentially affecting bacterial invasion through caveolae/lipid rafts.

In addition to its endosomal escape effect, platycodin D also synergizes with ribosomal inactivation protein to induce apoptosis in hepatoma cells through AKT and MAPK signaling pathways.

Platycodin D, polygalacin D, and PD2 from Platycodonis Radix enhance the anti-tumor activity of MHBP in hepatoma cells by promoting endosomal escape without affecting the cell membrane integrity.

Cholesterol synthesis inhibition or depletion in axon regeneration

Cholesterol depletion and inhibition, as well as its synthesis, can enhance axon regeneration, potentially through disruptions in axon growth inhibitor signaling and neuronal survival signaling processes.

One Raft to Guide Them All, and in Axon Regeneration Inhibit Them

Stable lipid rafts and their composition are crucial for axon regeneration and rebuilding functional neural circuits after damage.