Brain damage results in down-regulation of N-acetylaspartate as a neuronal osmolyte
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N-acetyl-l-aspartate (NAA) is present in the vertebrate brain, where its concentration is one of the highest of all free amino acids. Although NAA is synthesized and stored primarily in neurons, it is not hydrolyzed in these cells. However, after its regulated release into extracellular fluid, neuronal NAA is hydrolyzed by amidohydrolase II that is present in oligodendrocytes. About 30% of neurons do not contain appreciable amounts of NAA, but its prominence in 1H nuclear magnetic resonance spectroscopic (MRS) studies has led to its wide use as a neuronal marker in diagnostic human medicine as both an indicator of brain pathology, and of disease progression in a variety of central nervous system (CNS) diseases. Loss of NAA has been interpreted as indicating either loss of neurons, or loss of neuron viability. In this investigation, the upregulation of NAA in early stages of construction of the CNS, and its downregulation in experimentally induced damage models of the CNS is reported. The results of this study indicate that the buildup of NAA is not required for viability of neurons in monocellular cultures, and that NAA is lost from multicellular cultured brain slice explants that contain viable neurons. Thus, loss of NAA does not necessarily indicate either loss of neurons or their function. The NAA system, when present in the brain, appears to reflect a high degree of cellular integration, and therefore may be a unique metabolic construct of the intact vertebrate brain.
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- Brain damage results in down-regulation of N-acetylaspartate as a neuronal osmolyte
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- 1. Nathan S. Kline Institute for Psychiatric Research, Center for Neurochemistry, 140 Old Orangeburg Road, 10962, Orangeburg, New York, USA
- 2. New York State Psychiatric Institute and Columbia University College of Physicians and Surgeons, 1051 Riverside Drive, 10032, New York, NY, USA
- 3. MRC Clinical Sciences Centre, ICSM, Hammersmith Hospital Campus, Du Cane Road, WI2 ONN, London, England, UK
- 4. New York University School of Medicine, 550 First Avenue, New York, NY, USA