A comparison of model-based (2D) and design-based (3D) stereological methods for estimating cell number in the substantia nigra pars compacta (SNpc) of the C57BL/6J mouse.

The substantia nigra pars compacta (SNpc) is a compact brain structure that contains a variable distribution of cells in both medial to lateral and rostral to caudal dimensions. The SNpc is the primary brain structure affected in Parkinson's disease, where loss of dopaminergic neurons is one of the major hallmarks of the disorder. Neurotoxic and genetic models of Parkinson's disease, as well as mechanisms to treat this disorder, are modeled in the mouse. To accurately assess the validity of a model, one needs to be assured that the method(s) of analysis is accurate. Here, we determined the total number of dopaminergic neurons in the SNpc of the C57BL/6J mouse by serial reconstruction then compared that value to estimates derived using model-based stereology and design-based stereology. Serial reconstruction of the SNpc revealed the total number of SNpc dopaminergic neurons to be 8305+/-540 (+/-SEM). We compared this empirically derived neuron number to model based and design-based stereological estimates. We found that model based estimates gave a value of 8002+/-91 (+/-SEM) while design-based estimates were 8716+/-338 (+/-SEM). Statistical analysis showed no significant difference between estimates generated using model- or design-based stereological methods compared to empirically-derived counts using serial reconstruction.