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α-Synuclein Promotes Maturation of Immature Juxtaglomerular Neurons in the Mouse Olfactory Bulb

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Abstract

α-Synuclein (αSyn), the major constituent of Lewy bodies and Lewy neurites, is generally expressed in presynapses and is involved in synaptic function. However, we previously demonstrated that some neurons, including those in the olfactory bulb, show high αSyn expression levels in the cell body under normal conditions. αSyn is also known to be important for adult neurogenesis. Thus, in present study, we examined the role of αSyn in juxtaglomerular neurons (JGNs) with high αSyn expression in the mouse olfactory bulb. Most αSyn-enriched JGNs expressed sex-determining region Y-box 2 (Sox2), which functions to maintain neural immature identity. Interestingly, in αSyn homozygous (-/-) knockout (KO) mice, Sox2-positive JGNs were significantly increased compared with heterozygous (+/-) KO mice. Following global brain ischemia using wild-type mice, there was also a significant decrease in Sox2-positive JGNs, and in the co-expression ratio of Sox2 in αSyn-enriched JGNs. By contrast, the co-expression ratio of neuronal nuclei (NeuN, mature neuronal marker) was significantly increased in αSyn-enriched JGNs. However, this ischemia-induced decrease of Sox2-positive JGNs was not observed in αSyn homozygous KO mice. Overall, these data suggest that αSyn functions to promote the maturation of immature JGNs in the mouse olfactory bulb.

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Acknowledgments

We thank Professor Kanji Yoshimoto (Department of Food Sciences and Biotechnology, Faculty of Life Sciences, Hiroshima Institute of Technology, Japan) for instruction on basic surgical techniques for the two-vessel occlusion model.

Funding

This study was supported by a scientific research grant from the Japan Society for Promotion of Science (KT; Grant number 16K21283).

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Authors and Affiliations

  1. Department of Anatomy and Neurobiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto, 602-8566, Japan

    Katsutoshi Taguchi & Masaki Tanaka

  2. Department of Basic Geriatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto, 602-8566, Japan

    Yoshihisa Watanabe & Atsushi Tsujimura

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  1. Katsutoshi Taguchi
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  2. Yoshihisa Watanabe
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Contributions

KT and MT: conceived and designed the experiments, and wrote the manuscript; KT: performed the experiments; YW and AT: contributed to data analysis and discussion.

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Correspondence to Masaki Tanaka.

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This article does not contain any studies with human participants performed by any of the authors. Animal experiments were performed in accordance with the Guidelines for Animal Experiments, Kyoto Prefectural University of Medicine and national regulations as described in the section of materials and methods.

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Taguchi, K., Watanabe, Y., Tsujimura, A. et al. α-Synuclein Promotes Maturation of Immature Juxtaglomerular Neurons in the Mouse Olfactory Bulb. Mol Neurobiol 57, 1291–1304 (2020). https://doi.org/10.1007/s12035-019-01814-3

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