The Effects of Lithium Chloride and Other Substances on Levels of Brain N-Acetyl-L-Aspartic Acid in Canavan Disease-Like Rats
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Canavan disease (CD) is a human early-onset leukodystrophy, genetic in nature and resulting from an autosomally inherited recessive trait. CD is characterized by loss of the axon's myelin sheath, while leaving the axons intact, and spongiform degeneration, especially in white matter. It is an osmotic disease that affects both gray and white matter and is caused by the inability of oligodendrocytes to hydrolyze N-acetyl-L-aspartate (NAA) because of a lack of aspartoacylase activity. As a result, there is a build-up of NAA in brain with both cellular and extracellular edema, as well as NAA acidemia and NAA aciduria. Recent studies have indicated that several compounds have the ability to reduce brain levels of NAA in normal mice and rats. In this investigation, these compounds have been tested, using a CD-like rat model of the human disease to evaluate their potential for use in the treatment of the disease. Of seven substances tested in an acute 5-day study, only lithium chloride treatment resulted in a significant reduction of about 13% in whole-brain NAA levels in the CD-like rat model. This is the first pharmacological investigation of the effect of drugs on the level of brain NAA in an animal model of CD, and the first report of a substance that can reduce the brain NAA level in this model.
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- The Effects of Lithium Chloride and Other Substances on Levels of Brain N-Acetyl-L-Aspartic Acid in Canavan Disease-Like Rats
Volume 27, Issue 5 , pp 403-406
- Cover Date
- Print ISSN
- Online ISSN
- Kluwer Academic Publishers-Plenum Publishers
- Additional Links
- Canavan disease
- lithium chloride
- spongiform leukodystrophy
- Industry Sectors
- Author Affiliations
- 1. Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, New York, 10962
- 2. Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University Sakyo-Ku, Kyoto, 606-8501, Japan
- 3. New York State Psychiatric Institute and Columbia University College of Physicians and Surgeons, 1051 Riverside Drive, New York, New York, 10032