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

Mol Neurobiol. 2020 Mar;57(3):1291-1304. doi: 10.1007/s12035-019-01814-3. Epub 2019 Nov 13.

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.

Keywords: Ischemia; Juxtaglomerular neurons; Neuronal maturation; Olfactory bulb; α-Synuclein.

MeSH terms

  • Animals
  • Brain / metabolism
  • Lewy Bodies / metabolism
  • Mice, Knockout
  • Neural Stem Cells / metabolism*
  • Neurogenesis / physiology
  • Neurons / metabolism*
  • Olfactory Bulb / metabolism*
  • Synapses / metabolism
  • alpha-Synuclein / genetics
  • alpha-Synuclein / metabolism*

Substances

  • Snca protein, mouse
  • alpha-Synuclein