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

• Published in: The Journal of neuroscience Vol. 15; no. 11; pp. 7727 - 7733
• Main Authors: Sagot, Y, Dubois-Dauphin, M, Tan, SA, de Bilbao, F, Aebischer, P, Martinou, JC, Kato, AC
• Format: Journal Article
• Language: English
• Published: United States Soc Neuroscience 01.11.1995; Society for Neuroscience
• Subjects: 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 Proteins - genetics; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-bcl-2
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/jneurosci.15-11-07727.1995

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.