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Publication : The neurotoxin MPTP increases calbindin-D28k levels in mouse midbrain dopaminergic neurons.

First Author  Ng MC Year  1996
Journal  Brain Res Mol Brain Res Volume  36
Issue  2 Pages  329-36
PubMed ID  8965654 Mgi Jnum  J:32238
Mgi Id  MGI:79722 Doi  10.1016/0169-328x(95)00266-u
Citation  Ng MC, et al. (1996) The neurotoxin MPTP increases calbindin-D28k levels in mouse midbrain dopaminergic neurons. Brain Res Mol Brain Res 36(2):329-36
abstractText  The calcium-binding protein calbindin-D28k (CALB) has been localized in high concentrations in several neuronal populations within the central nervous system (CNS) and is believed to act as an intracellular calcium (Ca2+) buffer. There has been much interest and speculation concerning its potential neuroprotective function. However, there is little direct evidence linking CALB content of individual neurons to Ca2+ buffering ability, resistance to Ca(2+)-mediated excitotoxicity, or vulnerability to Ca(2+)-mediated degeneration. It is necessary to demonstrate these relationships on a cellular level so that more definitive conclusions can be made. We have utilized immunocytochemical and Western blot techniques to determine whether cellular CALB content is altered in the nucleus A10 dopaminergic region of the midbrain following administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Our data demonstrate a significant increase in the CALB content of nucleus A10 neurons (up to 227 +/- 23% above control) 3 and 6 h after MPTP treatment. CALB elevation demonstrated both time and dosage dependence as 6-h groups exhibited larger increases than 3-h groups, and a 60 mg/kg dosage induced a larger increase than a 20 mg/kg dosage. These data support the hypothesis that MPTP is neurotoxic by causing increases in free intracellular Ca2+ and that increased CALB in the midbrain dopaminergic neurons is a protective response to elevated intracellular free Ca2+.
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