Investigation of the effect of alpha melanocyte stimulating hormone on olfactory mechanisms and treatment in rats with induced olfactory dysfunction

Objective: Olfactory disorders occur in many diseases such as upper respiratory tract infections, head traumas and neurodegenerative diseases. Especially with the Covid-19 pandemic, the effects of loss of sense of smell on human health and quality of life have become remarkable. Although olfactory disorders are common worldwide, there is insufficient information about their pathophysiology and treatment. In this study, the effects of Alpha Melanocyte Stimulating Hormone (α-MSH) on neurogenesis and NGF, BDNF, IL-10 expressions in olfactory epithelium (OE), olfactory bulb (OB) and subventricular zone (SVZ) in peripheral olfactory disorder were examined and the possible role of α-MSH in olfactory mechanisms and treatment was investigated. Method: 48 male Sprague Dawley rats were divided into 8 groups. In order to create an odor impairment model, half of the rats received intranasal 10% zinc sulfate and the other half received intranasal saline. Half of the rats given intranasal zinc sulfate/saline received α-MSH (5 mg/kg) and the other half received saline intraperitoneally. The experiment was ended after 4 and 21 days of α-MSH/saline administration. Olfactory senses of all rats were evaluated by performing buried food and odor discrimination tests at the beginning of the experiment (T0), after zinc sulfate/saline administration (T1) and 1 day before euthanasia (T2). After blood samples were taken from the rats, nasal and brain tissues were isolated by perfusing with 4% paraformaldehyde. Blood samples were analyzed by ELISA method and nasal and brain tissues were analyzed by immunohistochemistry/immunofluorescence methods. Results: In our study, it was found that 21-day α-MSH treatment (KB+α-MSH group) in rats with olfactory dysfunction (OD) showed an ameliorative effect on OE damage compared to the OD group. KB+α-MSH group was found to have positive effects on OE neurogenesis by inducing an upward trend in ASCL1+, GAP-43+ and OMP+ immunoreactivities. IL-10+ immunoreactivity of KB+α-MSH group was found to be higher than the control group. In the KB+α-MSH group, there was no upward trend in NGF+ and BDNF+ immunoreactivity on days 4 and 21 compared to the KB group. Nestin/ASCL1 immunoreactivity in the SVZ of rats in the KB+α-MSH group showed an increasing trend on days 4 and 21 compared to the rats in the KB group, while DCX+ immunoreactivity showed a decreasing trend. In OB, NeuN+ immunoreactivity in the KB+α-MSH group tended to increase on day 4 and showed a significant decrease on day 21 compared to the KB group. In the KB+α-MSH group, better results were obtained in odor tests, especially on day 21. Conclusion: 21-day α-MSH treatment may positively affect OE neurogenesis by increasing stem cells, immature neurons and mature neurons in OE. The effect of α-MSH on OE neurogenesis may be direct and/or indirect through its anti-inflammatory effects. α-MSH may also affect SVZ neurogenesis and mature neurons in the OB, exhibiting positive effects in peripheral olfactory disorder.