Bcl-2 overexpression prevents motoneuron cell body loss but not axonal degeneration in a mouse model of a neurodegenerative disease

J Neurosci. 1995 Nov;15(11):7727-33. doi: 10.1523/JNEUROSCI.15-11-07727.1995.

Abstract

Bcl-2 and its analogs protect different classes of neurons from apoptosis in several experimental situations. These proteins may therefore provide a means for treatment of neurodegenerative diseases. We examined the effects of Bcl-2 overexpression in a genetic mouse model with motor neuron disease (progressive motor neuronopathy/pmn). Pmn/pmn mice lose motoneurons and myelinated axons, and die at 6 weeks of age. When these mice were crossed with transgenic mice that overexpress human Bcl-2, there was a rescue of the facial motoneurons with a concomitant restoration of their normal soma size and expression of choline acetyltransferase. However, Bcl-2 overexpression did not prevent degeneration of myelinated axons in the facial and phrenic motor nerves and it did not increase the life span of the animals. Since Bcl-2 acts strictly on neuronal cell body survival without compensating for nerve degeneration in pmn/pmn/bcl-2 mice, this proto-oncogene would not in itself be sufficient for treatment of neurodegenerative diseases where axonal impairment is a major component.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / physiology*
  • Cell Death
  • Facial Nerve / pathology
  • Humans
  • Immunohistochemistry
  • Mice
  • Mice, Transgenic
  • Motor Neuron Disease / metabolism*
  • Motor Neuron Disease / pathology*
  • Motor Neurons / pathology*
  • Nerve Degeneration*
  • Phrenic Nerve / pathology
  • Pons / pathology
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-bcl-2

Substances

  • MAS1 protein, human
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2