The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Alteration of Striatal Tetrahydrobiopterin in Iron-Induced Unilateral Model of Parkinson's Disease

  • Aryal, Bijay (Department of Pharmacology, College of Medicine, Dankook University) ;
  • Lee, Jin-Koo (Department of Pharmacology, College of Medicine, Dankook University) ;
  • Kim, Hak Rim (Department of Pharmacology, College of Medicine, Dankook University) ;
  • Kim, Hyung-Gun (Department of Pharmacology, College of Medicine, Dankook University)
  • Received : 2013.11.20
  • Accepted : 2014.02.05
  • Published : 2014.04.30
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Abstract

It has been suggested that transition metal ions such as iron can produce an oxidative injuries to nigrostriatal dopaminergic neurons, like Parkinson's disease (PD) and subsequent compensative increase of tetrahydrobiopterin ($BH_4$) during the disease progression induces the aggravation of dopaminergic neurodegeneration in striatum. It had been established that the direct administration of $BH_4$ into neuron would induce the neuronal toxicity in vitro. To elucidate a role of $BH_4$ in pathogenesis in the PD in vivo, we assessed the changes of dopamine (DA) and $BH_4$ at striatum in unilateral intranigral iron infused PD rat model. The ipsistriatal DA and $BH_4$ levels were significantly increased at 0.5 to 1 d and were continually depleting during 2 to 7 d after intranigral iron infusion. The turnover rate of $BH_4$ was higher than that of DA in early phase. However, the expression level of GTP-cyclohydrolase I mRNA in striatum was steadily increased after iron administration. These results suggest that the accumulation of intranigral iron leads to generation of oxidative stress which damage to dopaminergic neurons and causes increased release of $BH_4$ in the dopaminergic neuron. The degenerating dopaminergic neurons decrease the synthesis and release of both $BH_4$ and DA in vivo that are relevance to the progression of PD. Based on these data, we propose that the increase of $BH_4$ can deteriorate the disease progression in early phase of PD, and the inhibition of $BH_4$ increase could be a strategy for PD treatment.

Keywords

References

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