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.