MIDBRAIN DOPAMINERGIC-NEURONS IN THE MOUSE THAT CONTAIN CALBINDIN-D-28K EXHIBIT REDUCED VULNERABILITY TO MPTP-INDUCED NEURODEGENERATION

The calcium-binding protein calbindin-D-28k (CB) is located in midbrai n dopaminergic (DA) neurons that are less vulnerable to degeneration i n Parkinson's disease and in an animal model of the disorder, the MPTP -treated monkey. The present study sought to determine whether CB-cont aining DA neurons are also less vulnerable to degeneration in the MPTP -treated mouse. Double-labelling immunocytochemical staining and compu ter imaging techniques were employed to map and quantify the tyrosine hydroxylase-, CB- and CB-containing tyrosine hydroxylase neurons in po rtions of nucleus A9 and nucleus A10 (ventral tegmental area and centr al linear nucleus) following MPTP treatment in the C57BL/6 mouse. A cu mulative dose of 140 mg/kg MPTP produced a significantly greater loss of DA neurons that lack CB in both nucleus A9 (71 +/- 4%) and the vent ral tegmental area (70 +/- 4%), compared to the loss of DA neurons tha t contain CB (44 +/- 6% and 25 +/- 14%, respectively). In the central linear nucleus there was no loss of CB-containing DA neurons. These da ta demonstrate that the presence of CB in midbrain DA neurons identifi es a population of cells in the mouse that are less vulnerable to MPTP -induced degeneration. The mouse, therefore, can serve as a useful mod el in which to investigate the putative neuroprotective effects of CB in an animal model of Parkinson's disease. (C) 1996 Academic Press Lim ited