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Neurodegeneration in the animal model of Menkes' disease involves Bcl-2-linked apoptosis

L Rossi1, A De Martino, E Marchese

  • 1Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, 00133 Rome, Italy. luisa.rossi@uniroma2.it

Neuroscience
|April 20, 2001
PubMed

Insights

Copper deficiency in mice models of Menkes' disease causes brain cell death. This neurodegeneration is linked to mitochondrial dysfunction and reduced anti-apoptotic protein Bcl-2 expression.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Genetics

Background:

  • Copper is vital for brain development, function, and survival.
  • Disruptions in copper homeostasis are implicated in neurodegenerative diseases.
  • The precise molecular mechanisms linking copper to neurodegeneration remain unclear.

Purpose of the Study:

  • To investigate the molecular mechanisms of neurodegeneration in mottled/brindled mutant (Mo(br/y)) mice, an animal model for Menkes' disease.
  • To analyze the role of copper deficiency in apoptosis and energy metabolism in the brain.

Main Methods:

  • Morphological analysis of brain sections from Mo(br/y) mice.
  • Biochemical assays to measure copper content, enzyme activities (cytochrome c oxidase, copper-zinc-superoxide dismutase), glutathione, and ATP levels.
  • Western blot analysis to assess Bcl-2 expression and cytochrome c release.

Main Results:

  • Mo(br/y) mice exhibited increased apoptotic cells in the neocortex and hippocampus.
  • Decreased copper levels, cytochrome c oxidase activity, and ATP levels were observed in the brain.
  • Down-regulation of the anti-apoptotic protein Bcl-2 and increased cytochrome c release from mitochondria were detected.

Conclusions:

  • Copper depletion in Mo(br/y) mice leads to neurodegeneration.
  • Mitochondrial damage and impaired energy metabolism contribute to apoptosis.
  • Reduced Bcl-2 expression is a key factor in copper deficiency-induced neurodegeneration during brain development.

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