Tetrahydrobiopterin (BH4)-Mediated Neuronal Death Following Intrastriatal Kainic Acid: Implications for Parkinson’s Disease

Parkinson’s disease is characterized by progressive, premature death of dopamine neurons in the pars compacta of the substantia nigra (1–3). Clinical symptoms appear when dopamine neuronal death reaches 50–60% and there is loss of 70–80% of striatal dopamine (4). The profile of dopamine neuronal death in Parkinson’s disease is progressive (5, 6), and it is thought that, after diagnosis, there is continued, gradual neuronal death over the remaining lifespan of the patient (7). Animal models of Parkinson’s disease have been developed to study mechanisms underlying nigral neuronal death and provide insights into the etiology of Parkinson’s disease. Here, we report a rat model that exhibits progressive death of nigral neurons following unilateral injection of kainic acid in the striatum. Further, we demonstrate the utility of this model to study mechanisms underlying nigral dopamine neuronal death and suggest a possible role for tetrahydrobiopterin (BH4) in long-term death of these neurons.