IL-1β/IL-1R1 signaling induced by intranasal lipopolysaccharide infusion regulates alpha-Synuclein pathology in the olfactory bulb, substantia nigra and striatum.

Brain Pathology
Haichen NiuRongli Yang

Abstract

Olfactory dysfunction is one of the early symptoms seen in Parkinson's disease (PD). However, the mechanisms underlying olfactory pathology that impacts PD disease progression and post-mortem appearance of alpha-Synuclein (α-Syn) inclusions in and beyond olfactory bulb in PD remain unclear. It has been suggested that environmental toxins inhaled through the nose can induce inflammation in the olfactory bulb (OB), where Lewy body (LB) is the first to be found, and then, spread to related brain regions. We hypothesize that OB inflammation triggers local α-Syn pathology and promotes its spreading to cause PD. In this study, we evaluated this hypothesis by intranasal infusion of lipopolysaccharides (LPS) to induce OB inflammation in mice and examined cytokines expression and PD-like pathology. We found intranasal LPS-induced microglia activation, inflammatory cytokine expression and α-Syn overexpression and aggregation in the OB via interleukin-1β (IL-1β)/IL-1 receptor type I (IL-1R1) dependent signaling. In addition, an aberrant form of α-Syn, the phosphorylated serine 129 α-Syn (pS129 α-Syn), was found in the OB, substantia nigra (SN) and striatum 6 weeks after the LPS treatment. Moreover, 6 weeks after the LPS treatment, mice sh...Continue Reading

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Citations

Dec 10, 2020·International Journal of Molecular Sciences·Jolene Su Yi TanEng-King Tan
Jul 30, 2021·Ageing Research Reviews·Xiuli DanVilhelm A Bohr
Apr 16, 2021·Brain : a Journal of Neurology·Qing WangSven Pettersson

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Methods Mentioned

BETA
genotyping
transgenic
environmental stress
dissection
electrophoresis

Software Mentioned

ImageJ
Image EP
SPSS16
Waters Empower

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