Midbrain dopaminergic neurons in the mouse that contain calbindin-D28k exhibit reduced vulnerability to MPTP-induced neurodegeneration.
The calcium-binding protein calbindin-D28k (CB) is located in midbrain dopaminergic (DA) neurons that are less vulnerable to degeneration in Parkinson's disease and in an animal model of the disorder, the MPTP-treated monkey. The present study sought to determine whether CB-containing DA neurons are also less vulnerable to degeneration in the MPTP-treated mouse. Double-labelling immunocytochemical staining and computer imaging techniques were employed to map and quantify the tyrosine hydroxylase-, CB- and CB-containing tyrosine hydroxylase neurons in portions of nucleus A9 and nucleus A10 (ventral tegmental area and central linear nucleus) following MPTP treatment in the C57BL/6 mouse. A cumulative 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 ventral tegmental area (70 +/- 4%), compared to the loss of DA neurons that contain CB (44 +/- 6% and 25 +/- 14%, respectively). In the central linear nucleus there was no loss of CB-containing DA neurons. These data demonstrate that the presence of CB in midbrain DA neurons identifies a population of cells in the mouse that are less vulnerable to MPTP-induced degeneration. The mouse, therefore, can serve as a useful model in which to investigate the putative neuroprotective effects of CB in an animal model of Parkinson's disease.
Liang
C L
CL
Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas 75235-9070, USA.
Sinton
C M
CM
Sonsalla
P K
PK
German
D C
DC
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D064092:Calbindin 1; D064026:Calbindins; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
C576499:Calb1 protein, mouse; D064092:Calbindin 1; D064026:Calbindins; D015259:Dopamine Agents; D064030:S100 Calcium Binding Protein G; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine