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

May C. Ng, Anthony M. Iacopino, E. Matthew Quintero, Florentina Marches, Patricia K. Sonsalla, Chang Lin Liang, Samuel G. Speciale, Dwight C. German

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

The calcium-binding protein calbindin-D-28k (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 Ca2+-mediated excitotoxicity, or vulnerability to Ca2+-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+.

Original languageEnglish (US)
Pages (from-to)329-336
Number of pages8
JournalMolecular Brain Research
Volume36
Issue number2
DOIs
StatePublished - Mar 1996

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Keywords

  • Calbindin-D
  • Dopaminergic neuron
  • Immunocytochemistry
  • MPTP
  • Midbrain
  • Mouse
  • Neurodegeneration
  • Western blot

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