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 syndrome for numerous neurodegenerative diseases. Neuroinflammation and neurodegenerative processes in the olfactory bulbs (OB) may be initiated by infectious agents in the nasal cavity, particularly by bacterial lipopolysaccharide (LPS). The molecular mechanisms mediating the effect of this endotoxin on OB remain poorly understood. AIM: to study the effect of different doses of intranasally administered LPS on the intensity of immunopositive staining of the olfactory epithelium with antibodies to alpha-synuclein (A-syn) and MyD88, as well as OB cells with antibodies to A-syn and GFAP. METHODS: Eighteen male BALB/C mice (20–33 g) were used in the study. The animals received daily unilateral intranasal injections of sterile saline (control) or LPS in high (0.1 μg/ml) or low concentration (0.01 μg/ml) in a volume of 10 μl. After 28 days of the experiment, the brains and nasal passages were frozen using dry ice. Serial cryostat sections (14 μm) were prepared and stained with methylene blue and antibodies to A-syn, MyD88, and GFAP. The labeling intensity of immunopositive structures was quantitatively assessed using ImagePro Inside 8.0. RESULTS: Unilateral intranasal administration of LPS solution in mice resulted in a significant dose-dependent elevation of immunopositive А-syn levels in olfactory receptor cells, olfactory nerve bundles, and glomeruli of the OB. Additionally, there was a dose-dependent increase in the expression of MyD88 in olfactory epithelium and GFAP in the OB glomerular area on the side of endotoxin administration. CONCLUSION: The observed morphological and immunohistochemical changes after intranasal administration of LPS indicate the development of dose-dependent neuroinflammation in the OB, which is initiated by increased expression of A-syn and MyD88 in the olfactory epithelium.