Department of Anatomy and Neurobiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto, 602-8566, Japan.
Department of Basic Geriatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto, 602-8566, Japan.
Mol Neurobiol. 2020 Mar;57(3):1291-1304. doi: 10.1007/s12035-019-01814-3. Epub 2019 Nov 13.
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.
α-突触核蛋白(αSyn)是路易体和路易神经纤维的主要成分,通常表达于突触前,参与突触功能。然而,我们之前的研究表明,包括嗅球中的一些神经元在内,在正常情况下,细胞体中存在高水平的 αSyn 表达。αSyn 对于成体神经发生也很重要。因此,在本研究中,我们检查了在表达高水平 αSyn 的嗅球中具有高 αSyn 表达的肾小球旁细胞(JGN)中的 αSyn 作用。大多数富含 αSyn 的 JGN 表达性别决定区 Y 框 2(Sox2),其功能是维持神经未成熟状态。有趣的是,在 αSyn 纯合子(-/-)敲除(KO)小鼠中,Sox2 阳性 JGN 数量明显多于杂合子(+/-)KO 小鼠。在使用野生型小鼠进行全脑缺血后,Sox2 阳性 JGN 数量也明显减少,而富含 αSyn 的 JGN 中 Sox2 的共表达比例也减少。相比之下,富含 αSyn 的 JGN 中神经元核(NeuN,成熟神经元标志物)的共表达比例明显增加。然而,在 αSyn 纯合子 KO 小鼠中未观察到这种缺血诱导的 Sox2 阳性 JGN 减少。总的来说,这些数据表明 αSyn 促进了小鼠嗅球中未成熟 JGN 的成熟。