Effect of the co-administration of vitamin C and vitamin E on tyrosine hydroxylase and Nurr1 expression in the prenatal rat ventral mesencephalon

J Vet Med Sci. 2008 Aug;70(8):791-7. doi: 10.1292/jvms.70.791.


Tyrosine hydroxylase (TH) is the rate-limiting enzyme of dopamine (DA) biosynthesis, which is up-regulated by vitamin C administration. Nurr1 gene is highly expressed in brain and important for midbrain DAergic cell development and survival. But, the role of vitamin C and/or vitamin E during Nurr1 expression is yet to be known. Further, the synergistic effect of vitamins C and E on TH expression has not yet been explored clinically. Therefore, we studied the effects of single or co- administration of vitamin C (0.5 mM) and vitamin E (1 mM) for 72 hr, on both TH and Nurr1 expression in in vitro primary cultured gestational days (GD) 13.5 rat ventral mesencephalon (VM) by Western blot and immunocytochemistry. Our study revealed highest expressions of both TH and Nurr1 in the vitamin C + vitamin E treated group. TH expression was also increased in the vitamin C treated group than that of the control group, but the vitamin E treated group did not show any statistically significant effect. However, both the vitamin C and the vitamin E treated groups revealed increased expression of Nurr1 protein as compared with the control group. The present experimental data suggest that vitamin C can up-regulate the protein expression of TH, but Nurr1 level was elevated either by vitamin C or by vitamin E administration. Further, vitamin E acts synergistically with vitamin C to elevate TH and Nurr1 expression, which is the most novel finding of our study and for the first time; we reported this result, since there have been no published data on the synergistic effect of both the antioxidant vitamins on TH and Nurr1 expression in VM. As the motor function defect due to the progressive loss of DAergic neuron is the major reason of Parkinsonism, therefore, the results of our study finally suggest the effective role of vitamin C and vitamin E during early treatment of Parkinsonism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ascorbic Acid / pharmacology*
  • Blotting, Western
  • Cells, Cultured
  • DNA-Binding Proteins / drug effects
  • DNA-Binding Proteins / metabolism*
  • Female
  • Mesencephalon / drug effects
  • Mesencephalon / embryology*
  • Mesencephalon / metabolism
  • Nuclear Receptor Subfamily 4, Group A, Member 2
  • Pregnancy
  • Rats
  • Transcription Factors / drug effects
  • Transcription Factors / metabolism*
  • Tyrosine 3-Monooxygenase / drug effects
  • Tyrosine 3-Monooxygenase / metabolism*
  • Vitamin E / pharmacology*


  • DNA-Binding Proteins
  • Nr4a2 protein, rat
  • Nuclear Receptor Subfamily 4, Group A, Member 2
  • Transcription Factors
  • Vitamin E
  • Tyrosine 3-Monooxygenase
  • Ascorbic Acid