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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2024

Open Access 01-12-2024 | Parkinson's Disease | Research

Nicotine restores olfactory function by activation of prok2R/Akt/FoxO3a axis in Parkinson’s disease

Authors: Qinglong Guo, Yi Wang, Liangchen Yu, Liao Guan, Xuefei Ji, Xiaohui Li, Gang Pang, Zhenhua Ren, Lei Ye, Hongwei Cheng

Published in: Journal of Translational Medicine | Issue 1/2024

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Abstract

Background

Olfactory dysfunction occurs frequently in Parkinson’s disease (PD). In this study, we aimed to explore the potential biomarkers and underlying molecular pathways of nicotine for the treatment of olfactory dysfunction in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD mice.

Methods

MPTP was introduced into C57BL/6 male mice to generate a PD model. Regarding in vivo experiments, we performed behavioral tests to estimate the protective effects of nicotine in MPTP-induced PD mice. RNA sequencing and traditional molecular methods were used to identify molecules, pathways, and biological processes in the olfactory bulb of PD mouse models. Then, in vitro experiments were conducted to evaluate whether nicotine can activate the prok2R/Akt/FoxO3a signaling pathway in both HEK293T cell lines and primary olfactory neurons treated with 1-methyl-4-phenylpyridinium (MPP+). Next, prok2R overexpression (prok2R+) and knockdown (prok2R−) were introduced with lentivirus, and the Akt/FoxO3a signaling pathway was further explored. Finally, the damaging effects of MPP+ were evaluated in prok2R overexpression (prok2R+) HEK293T cell lines.

Results

Nicotine intervention significantly alleviated olfactory and motor dysfunctions in mice with PD. The prok2R/Akt/FoxO3a signaling pathway was activated after nicotine treatment. Consequently, apoptosis of olfactory sensory neurons was significantly reduced. Furthermore, prok2R+ and prok2R− HEK293T cell lines exhibited upregulation and downregulation of the Akt/FoxO3a signaling pathway, respectively. Additionally, prok2R+ HEK293T cells were resistant to MPP+-induced apoptosis.

Conclusions

This study showed the effectiveness and underlying mechanisms of nicotine in improving hyposmia in PD mice. These improvements were correlated with reduced apoptosis of olfactory sensory neurons via activated prok2R/Akt/FoxO3a axis. These results explained the potential protective functions of nicotine in PD patients.
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Metadata
Title
Nicotine restores olfactory function by activation of prok2R/Akt/FoxO3a axis in Parkinson’s disease
Authors
Qinglong Guo
Yi Wang
Liangchen Yu
Liao Guan
Xuefei Ji
Xiaohui Li
Gang Pang
Zhenhua Ren
Lei Ye
Hongwei Cheng
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2024
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-024-05171-1

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