Characterisation of the Substantia Nigra Pars Compacta in the Absence of Neurturin

Abstract

Purpose- Neurturin, a member of the GDNF family, is a potent neurotrophic factor for dopaminergic cells and is currently being trialled as a therapy for Parkinson's disease patients. Previous analysis of neonatal neurturin knockout mice reported no gross abnormalities in the brain or any overt difference in tyrosine hydroxylase staining, however these analyses were qualitative. Here we show quantitative data on dopaminergic neurons of the substantia nigra in mice lacking neurturin. Methods- Sections from 12-14 week old neurturin knockout mouse brains and their wildtype littermates (n=3) were sequentially labelled through the substantia nigra pars compacta with tyrosine hydroxylase (TH) and calbindin antibodies. Cell numbers were quantified using fluorescence stereology. The number of cell processes and cell sizes were estimated by visualisation of 3D data sets. Results- No significant difference in the overall number of TH+ cells was found betweenknockout and wildtype mice. However, there was a significant increase in the number of TH+/calbindin+ cellsin the knockout mice as compared with their wildtype littermates. Conclusion- TH+/calbindin+ dopaminergicneurons of the substantia nigra have an increased survival potential in Parkinson's disease (Murase and McKay, 2006). Our results suggest a subtle change in the composition of the nigral dopaminergicneurons in the absence of neurturin, namely, the promoting of the TH+/calbindin+ cell phenotype in thesubstantia nigra pars compacta