Pro-Apoptotic Changes in Brain Mitochondria After Toxin Exposure

Abstract

Nitochondria normally function to provide sources of energy for vital cellular functions. However, under stressful conditions these organelles may trigger events that lead eventually to cell death. Thus, mitochondria have been implicated as major contributors to neuronal death in a variety of neurodegenerative disorders. In this report we describe functional changes in mitochondria measured in living brain tissue as a result of exposure to toxins thought to contribute to neurodegeneration. Mitochondrial NADH levels were shown to increase following treatment with l-methyl-4-phenylpyridium (MPP+) at times when neuronal electrophysiology was impaired. In addition, NPP+ appeared to cause oxidation of cytochrome b, providing further Support that this toxin inhibits Mitochondrial complex I. 3-nitropropionic acid (3-NP) also resulted in blockade of neuronal electrical activity but had minimal effects on mitochondrial NADH and redox activity of respiratory chain cytochromes. Both toxins produced delayed and selective cell death in hippocampal subfield CAl. Neurons in this subfield have been shown previously to be selectively vulnerable to hypoxia/ischemia. The data reported here suggest that these neurons may also be selectively vulnerable to mitochondrial toxins.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2000
Accession Number
ADA383069

Entities

People

  • Thomas J. Sick

Organizations

  • University of Miami

Tags

DTIC Thesaurus Topics

  • Absorption
  • Absorption Spectra
  • Animals
  • Brain
  • Cell Physiological Processes
  • Cells
  • Chemical Compounds
  • Cytochromes
  • Diseases And Disorders
  • Electrophysiological Phenomena
  • Laboratory Animals
  • Materials
  • Mitochondria
  • Neurodegeneration
  • Neurodegenerative Diseases
  • Recombinant Dna
  • Spectra

Fields of Study

  • Biology

Readers

  • Cellular and Molecular Pathways of Apoptosis.
  • Molecular and Cellular Biology
  • Neuroscience