Motor neurone metabolism

The cell and molecular mechanisms which determine the motor neurone (MN) ph enotype are unclear. Tissue culture models offer a unique system for the st udy of a wide variety of MN features. For instance, since the neurone-astro cyte metabolic interactions play a critical role in the selective MN loss o bserved in amyotrophic lateral sclerosis (ALS), the glutamatergic MN toxici ty could be reanalyzed in vitro, after a careful evaluation of the role of astrocytes. Ca2+ appears to be important in inducing MN loss from in vitro studies. It was shown primarily in culture that apoptotic or necrotic death of neurones after injury depends upon the cell energetic status. Alsb, SOD -1 mutations were successfully expressed in cultured MNs, providing a criti cal assay to sequence the molecular processes responsible for MN degenerati on due to an identified genetic defect. Purified human developing MNs and a strocytes were recently obtained from the spinal cord anterior horn. The ef fects of molecules affecting MN survival, neurite extension, and metabolism can easily be tested in long-term cultures. Interactions at the single cel l level can be studied today using a series of RNA amplification techniques . Understanding the properties of human MNs in vitro may represent a critic al tool in defining regional metabolic changes that could constitute the fi rst pathogenic event of cell degeneration in ALS. (C) 1999 Published by Els evier Science B.V. All rights reserved.