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Uric Acid Enhances Neurogenesis in a Parkinsonian Model by Remodeling Mitochondria

Authors
 Ji Eun Lee  ;  Yu Jin Shin  ;  Yi Seul Kim  ;  Ha Na Kim  ;  Dong Yeol Kim  ;  Seok Jong Chung  ;  Han Soo Yoo  ;  Jin Young Shin  ;  Phil Hyu Lee 
Citation
 FRONTIERS IN AGING NEUROSCIENCE, Vol.14 : 851711, 2022-06 
Journal Title
FRONTIERS IN AGING NEUROSCIENCE
Issue Date
2022-06
Keywords
Parkinson’s disease ; mitochondrial dynamics ; neural precursor cell ; neurogenesis ; uric acid
Abstract
Background: Adult 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.

Methods: We 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+).

Results: Uric 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.

Conclusion: In MPTP-induced parkinsonian model, UA probably enhanced neurogenesis via regulating mitochondrial dynamics, promoting fusion machinery, and inhibiting fission process.
Files in This Item:
T202204531.pdf Download
DOI
10.3389/fnagi.2022.851711
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
Yonsei Authors
Shin, Jin Young(신진영)
Yoo, Han Soo(유한수) ORCID logo https://orcid.org/0000-0001-7846-6271
Lee, Phil Hyu(이필휴) ORCID logo https://orcid.org/0000-0001-9931-8462
Chung, Seok Jong(정석종) ORCID logo https://orcid.org/0000-0001-6086-3199
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/191550
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