We have reported previously that tetrahydrobiopterin (BH4), an obligatory cofactor for dopamine synthesis, exerts preferential toxicity on dopamine producing cells. We report in the present study that BH4 injection into the lateral ventricle leads to degeneration of the dopaminergic terminals in the striatum, evidenced by a loss of tyrosine hydroxylase (TH) immunopositive fibers, a decreased amount of TH protein, and decreased dopamine content. Thus, the results of our study further provide evidence that BH4, the molecule endogenously present in the dopaminergic neurons, may participate in the nigrostriatal degeneration as in Parkinson's disease.
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