Grafts of Embryonic Dopamine Neurons in Rodent Models of Parkinson's Disease

Abstract

This chapter exemplifies rodent models of Parkinson's disease that have been used in transplantation studies and recounts basic transplantation methods. It describes morphological features of grafts containing dopamine neurons and focuses on the role of nigral grafts that are implanted homotopically in the mesencephalon, for example, near their location in the normal brain. The neurotoxin 6-hydroxydopamine (OHDA) is selectively taken up by catecholaminergic neurons and kills them through a mechanism that is still not fully elucidated, but may well include oxidative stress. When injected in adequate amounts into the brain, it can cause extensive and permanent damage to catecholaminergic neurons, such as those giving rise to the nigrostriatal pathway. The survival of dopamine neurons placed in a 6-OHDA denervated striatum is reflected by restoration of striatal dopamine levels to around 10 to 30% of normal. Examination of the ratio between levels of the dopamine metabolite DOPAC and dopamine reveals ratios that are 50 to 200% higher in grafted striata compared to normal, suggesting that the grafted neurons have an increased transmitter turnove