MPP+-induced pathophysiology demonstrates advantages of neurotoxicology studies in brain slices

Gary E. Hollinden, Juan R. Sanchez-Ramos, Thomas Sick, Myron Rosenthal

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Since MPTP and its metabolite MPP+ produce nigrostriatal lesions and symptoms similar to Parkinson's disease, recent studies have aimed toward defining their selectivity and neurotoxic mechanisms. In mitochondria in vitro, MPP+ blocked electron transport and decreased oxygen consumption. However, these effects were not selective to striatal mitochondria or even to mitochondria from brain, they required concentrations of MPP+ much greater than those found in vivo, and physiological actions could not be related to intramitochondrial changes. Lower doses of MPP+ did produce highly selective degeneration of dopaminergic (DA) neurons in cell cultures. We report here that MPP+ provoked large (80%) oxidations of cytochrome b and large Ko+ increments (approximately 30 mM) in rat striatal slices. These effects were slowed by mazindol, which inhibits DA uptake, and were markedly attenuated in rat hippocampal slices which have little DA input. Since DA terminals comprise only 2-4% of the striatal mass, the large MPP+-induced changes suggest that while MPP+ neurotoxicity in brain requires the presence of functioning DA terminals, effects are not confined to these terminals. Such studies illustrate the complexity of MPP+ neurotoxicity and demonstrate the importance of investigations in models such as brain slices with an extracellular space and intercellular relationships as in intact brain.

Original languageEnglish
Pages (from-to)51-57
Number of pages7
JournalJournal of Neuroscience Methods
Volume28
Issue number1-2
DOIs
StatePublished - Jan 1 1989

Fingerprint

Corpus Striatum
Mitochondria
Brain
Mazindol
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Dopamine Agents
Cytochromes b
Dopaminergic Neurons
Extracellular Space
Electron Transport
Oxygen Consumption
Parkinson Disease
Cell Culture Techniques

Keywords

  • Brain slice
  • Cytochrome b
  • Extracellular potassium
  • Hippocampal slice
  • MPP
  • MPTP
  • Striatal slice

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

MPP+-induced pathophysiology demonstrates advantages of neurotoxicology studies in brain slices. / Hollinden, Gary E.; Sanchez-Ramos, Juan R.; Sick, Thomas; Rosenthal, Myron.

In: Journal of Neuroscience Methods, Vol. 28, No. 1-2, 01.01.1989, p. 51-57.

Research output: Contribution to journalArticle

Hollinden, Gary E. ; Sanchez-Ramos, Juan R. ; Sick, Thomas ; Rosenthal, Myron. / MPP+-induced pathophysiology demonstrates advantages of neurotoxicology studies in brain slices. In: Journal of Neuroscience Methods. 1989 ; Vol. 28, No. 1-2. pp. 51-57.
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