Trophic factors differentiate dopamine neurons vulnerable to Parkinson’s disease

Abstract

Recent studies suggest a variety of factors characterize substantia nigra neurons vulnerable to Parkinson’s disease, including the transcription factors Pitx3 and Otx2 and the trophic factor receptor DCC, but there is limited information on their expression and localisation in adult humans. Pitx3, Otx2 and DCC were immunohistochemically localised in the upper brainstem of adult humans and mice and protein expression assessed using relative intensity measures and online microarray data. Pitx3 was present and highly expressed in most dopamine neurons. Surprisingly, in our elderly subjects no Otx2 immunoreactivity was detected in dopamine neurons, although Otx2 gene expression was found in younger cases. Enhanced DCC gene expression occurred in the substantia nigra, and higher amounts of DCC protein characterised vulnerable ventral nigral dopamine neurons. Our data show that, at the age when Parkinson’s disease typically occurs, there are no significant differences in the expression of transcription factors in brainstem dopamine neurons, but those most vulnerable to Parkinson’s disease rely more on the trophic factor receptor DCC than other brainstem dopamine neurons.