Abstract
Olfactory bulb, as one of sensory organs opening to the outside, is susceptible to toxic environment and easy to deteriorate. Recent studies in Parkinson’s disease (PD) patients and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys have shown that abnormal α-synuclein is accumulated in the olfactory glomeruli, suggesting that the lesions of PD are not only confined to the substantia nigra (SN) but also located in the olfactory bulb. Thus, olfactory bulb might be the region of onset in PD pathogenesis and a targeted region for diagnosis and treatment of PD. However, the relationship between olfactory bulb and pathogenesis of PD remains unclear. In the present study, we investigated the inflammatory pathological alterations in olfactory bulb and the underlying mechanisms in chronic MPTP mice. Mice were treated with MPTP/P, i.e., MPTP (25 mg/kg, s.c.) plus probenecid (250 mg/kg, i.p.) every 4 days, for ten times. The mice displayed typical parkinsonian syndrome. Then we examined their olfactory function and the pathologic changes in olfactory bulb. The mice showed obvious olfactory dysfunction in a buried pellet test. Immunohistochemical studies revealed that tyrosine hydroxylase (TH) protein levels were significantly decreased, whereas abnormal α-synuclein was significantly increased in the olfactory bulbs. Furthermore, the olfactory bulbs in MPTP/P-treated mice showed significantly increased levels of interleukin-1β (IL-1β), caspase-1, glial fibrillary acidic protein (GFAP), Toll receptor 4 (TLR4), phosphorylation of p65, as well as activated molecules of NOD-like receptor protein 3 (NLRP3) that were associated with neuroinflammation. Our results demonstrate that MPTP/P-caused olfactory bulb damage might be related to NLRP3-mediated inflammation.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (81573640, 81773925, and U1402221), the Beijing Natural Science Foundation (7161011), and Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education (P201701).
Author contributions
Y-hY and N-hC designed the research; YC, Q-sZ, Q-hS, SW, and H-bW performed the research; Q-hS, SW, and H-bW contributed analytic tools; YC and Q-sZ analyzed data; YC wrote the paper. All authors reviewed the manuscript.
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Chen, Y., Zhang, Qs., Shao, Qh. et al. NLRP3 inflammasome pathway is involved in olfactory bulb pathological alteration induced by MPTP. Acta Pharmacol Sin 40, 991–998 (2019). https://doi.org/10.1038/s41401-018-0209-1
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DOI: https://doi.org/10.1038/s41401-018-0209-1
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