Fluoxetine activated melanocyte stem cells in mice and zebrafish

Design

preclinical - melanocyte stem cell depletion mouse model, transgenic zebrafish, keratinocyte conditioned-medium experiments

Population

mice and zebrafish; narrow-band UVB as positive control

Primary outcome

epidermal melanocyte number and melanocyte stem cell activation

Effect

more epidermal melanocytes after 14 days in mice and 2 days in zebrafish, with HTR1A and Wnt7a upregulation and no detected oxidative stress or DNA damage

Melanocyte stem cells in the hair follicle are the reservoir that repigmentation in vitiligo depends on, and narrow-band UVB works partly by activating them - at the cost of oxidative stress and DNA damage. This study asked whether fluoxetine could do the same thing without that cost.

In a melanocyte stem cell depletion mouse model, 14 days of fluoxetine was associated with more epidermal melanocytes, with follicular stem cell activation appearing one to three days after treatment. A transgenic zebrafish model showed the same after two days. At the timepoints studied, fluoxetine produced no oxidative stress, DNA damage, apoptosis or inflammation in mouse skin, while narrow-band UVB - used as the positive control - did. Mechanistically, HTR1A and Wnt7a colocalised in hair germ epithelial cells, and conditioned medium from fluoxetine-treated keratinocytes activated Wnt signalling in melanoma cells, indicating the effect on melanocytes is indirect and routed through the epithelium.

This is preclinical and should be read that way. There is no human vitiligo data here, no dosing, and a drug already widely prescribed - which creates an obvious temptation. Fluoxetine is not a repigmentation treatment, and a patient taking it for depression should not be told it will help their vitiligo. The value is that it identifies an epithelial serotonin-Wnt route to stem cell activation that does not require ultraviolet exposure.

• Do not prescribe or recommend fluoxetine for vitiligo - there is no human efficacy evidence
• Continue narrow-band UVB as the phototherapy standard where it is indicated and available
• If a vitiligo patient is already on an SSRI for a mood disorder, there is no reason to change it either way
• Note that the comparison was against narrow-band UVB in mice, not against any treatment in people

Why it matters

It separates melanocyte stem cell activation from ultraviolet exposure, which is the limiting cost of every current repigmentation strategy.

Don't overread it

Mouse and zebrafish models with no human data - and the drug's ready availability makes premature use the obvious risk here.

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