Alpha-melanocyte-stimulating hormone promotes functional recovery in peripheral olfactory dysfunction by modulating bulbar neuroinflammation and enhancing neuronal maturation.

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.