Dose-dependent effects of intranasal lipopolysaccharide administration on alpha-synuclein levels in the olfactory epithelium and neuroinflammation in the olfactory bulbs of mice

BACKGROUND: Olfactory dysfunction is a prodromal symptom of many neurodegenerative diseases. Neuroinflammatory and neurodegenerative processes in the olfactory bulbs may be initiated by infectious agents in the nasal cavity, particularly bacterial lipopolysaccharide (LPS). The molecular mechanisms mediating the effects of this endotoxin on the olfactory epithelium and the development of pathological processes in the olfactory bulbs remain insufficiently studied. AIM: This study aimed to investigate the effects of different doses of intranasally administered lipopolysaccharide on the intensity of immunopositive staining of the olfactory epithelium with antibodies against alpha-synuclein (α-syn) and the adaptor protein MyD88, as well as of olfactory bulbs with antibodies against α-syn and glial fibrillary acidic protein (GFAP). METHODS: The study included 18 male BALB/c mice weighing 20–33 g. Animals received unilateral intranasal injections of sterile saline 10 μL daily (control) or lipopolysaccharide at a high (0.1 μg/mL) or low (0.01 μg/mL) concentration. After 28 days, the brains and nasal structure complexes were excised and frozen using dry ice. Serial cryostat sections (14 μm) were prepared and stained with methylene blue and antibodies against α-syn, MyD88, and GFAP. The intensity of immunolabeling was quantitatively assessed using Image-Pro Insight 8.0 software. RESULTS: Unilateral intranasal administration of lipopolysaccharide solution to mice resulted in a dose-dependent increase in α-syn levels in receptor cells, olfactory nerve bundles, and olfactory bulb glomeruli, along with a dose-dependent increase in MyD88 in the receptor epithelium and GFAP in the glomerular layer of the olfactory bulb ipsilateral to endotoxin administration. CONCLUSION: The observed morphological and immunohistochemical changes in the olfactory bulbs following intranasal lipopolysaccharide administration indicate the development of dose-dependent neuroinflammation in the glomerular layer. Neuroinflammation in the olfactory bulb appears to be initiated by LPS-induced upregulation of α-syn expression in receptor neurons projecting to the bulbs, mediated by activation of MyD88, which participates in intracellular signaling downstream of Toll-like receptors and interleukin-1 receptor family members.