Fig. 5. Similar distribution of MesDA neuronal losses in ak mice and in individuals with Parkinson's disease (PD). (A) The right midbrain of a normal mouse showing the distribution of TH-positive Pitx3-positive (green with red core) and TH-positive Pitx3-negative neurons (green) in SNc and VTA. Most ventral SNc TH-positive neurons are Pitx3 positive, whereas the dorsal SNc largely contains Pitx3-negative TH-positive neurons. About half of the VTA TH-positive neurons are Pitx3 positive, and both populations are intermingled. (B) In ak mice, SNc Pitx3-positive neurons are lost between E12.5 and P1, whereas VTA cells are lost postnatally. (C) Outline of the right MesDA system of a normal human showing the distribution of TH-positive neurons in SNc and VTA. (D) Individuals with PD typically have the most severe cell depletion in ventral SNc, followed by dorsal SNc and VTA [modified, with permission, from Jellinger (Jellinger, 2001)]. Although a decrease of PITX3-positive neurons was shown in samples from individuals with PD (Smidt et al., 1997), the regional distribution of human PITX3-positive neurons remains to be established.