Frontiers in Aging Neuroscience (Jun 2022)

Uric Acid Enhances Neurogenesis in a Parkinsonian Model by Remodeling Mitochondria

  • Ji Eun Lee,
  • Yu Jin Shin,
  • Yi Seul Kim,
  • Ha Na Kim,
  • Dong Yeol Kim,
  • Seok Jong Chung,
  • Han Soo Yoo,
  • Jin Young Shin,
  • Jin Young Shin,
  • Phil Hyu Lee,
  • Phil Hyu Lee

DOI
https://doi.org/10.3389/fnagi.2022.851711
Journal volume & issue
Vol. 14

Abstract

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BackgroundAdult neurogenesis is the process of generating new neurons to enter neural circuits and differentiate into functional neurons. However, it is significantly reduced in Parkinson’s disease (PD). Uric acid (UA), a natural antioxidant, has neuroprotective properties in patients with PD. This study aimed to investigate whether UA would enhance neurogenesis in PD.MethodsWe evaluated whether elevating serum UA levels in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonian mouse model would restore neurogenesis in the subventricular zone (SVZ). For a cellular model, we primary cultured neural precursor cells (NPCs) from post-natal day 1 rat and evaluated whether UA treatment promoted cell proliferation against 1-methyl-4-phenylpyridinium (MPP+).ResultsUric acid enhanced neurogenesis in both in vivo and in vitro parkinsonian model. UA-elevating therapy significantly increased the number of bromodeoxyuridine (BrdU)-positive cells in the SVZ of PD animals as compared to PD mice with normal UA levels. In a cellular model, UA treatment increased the expression of Ki-67. In the process of modulating neurogenesis, UA elevation up-regulated the expression of mitochondrial fusion markers.ConclusionIn MPTP-induced parkinsonian model, UA probably enhanced neurogenesis via regulating mitochondrial dynamics, promoting fusion machinery, and inhibiting fission process.

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