Alpha-melanocyte-stimulating hormone promotes functional recovery in peripheral olfactory dysfunction by modulating...

Although olfactory dysfunction (OD) is common worldwide, there is insufficient information about its pathophysiology and treatment. Alpha-melanocyte-stimulating hormone (α-MSH) has anti-inflammatory and neuroprotective properties and has been suggested to promote neurogenesis. This study investigated whether α-MSH improves regeneration, inflammatory responses, trophic factor expression, and olfactory behavior in a rat model of intranasal zinc sulfate (ZnSO₄) induced peripheral OD. Therefore, male Sprague Dawley rats were assigned to Control, OD, α-MSH, and OD+α-MSH groups and evaluated at days 4 and 21. Olfactory function was assessed using buried food and odor discrimination tests at baseline, after induction, and before euthanasia. Olfactory epithelium (OE) thickness and immunoreactivity for ASCL1, GAP-43, OMP, NGF, BDNF, TNF-α, and IL-10 were analyzed in the OE, olfactory bulb (OB), subventricular zone (SVZ), and hippocampal subgranular zone (SGZ), together with SVZ and SGZ neurogenesis markers (Nestin, ASCL1, DCX, NeuN). ZnSO₄ caused a marked reduction in OE thickness and OMP positivity, with increased ASCL1 and GAP-43 at both time points, confirming injury induced regeneration. α-MSH produced limited histological recovery at day 4 but promoted partial restoration of OE thickness and OMP immunoreactivity by day 21 and improved olfactory performance. SVZ neurogenesis markers were unchanged. In the OB, OD increased NeuN + cells, while α-MSH normalized NeuN and partially restored TNF-α and IL-10 expression by day 21. In the SGZ, α-MSH decreased ASCL1+ cells at day 21 without altering other markers. These findings indicate that α-MSH promotes recovery by modulating inflammation and epithelial maturation. It shows promise as a treatment for impaired olfaction.