Brain damage results in down-regulation of N-acetylaspartate as a neuronal osmolyte
Received: 10 October 2002 Accepted: 10 December 2002 DOI:
Cite this article as: Baslow, M.H., Suckow, R.F., Gaynor, K. et al. Neuromol Med (2003) 3: 95. doi:10.1385/NMM:3:2:95 Abstract 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. Index Entries N-acetyl- l-aspartate astrocytes brain canavan disease hypoacetylaspartia neurons oligodendrocytes References
Baslow M. H. and Resnik T. R. (1997) Canavan disease: Analysis of the nature of the metabolic lesions responsible for development of the observed clinical symptoms.
J. Mol. Neurosci.
Baslow M. H., Suckow R., Sapirstein V., and Hungund B. L. (1999) Expression of aspartoacylase activity in cultured rat macroglial cells is limited to oligodendrocytes.
J. Mol. Neurosci.
Baslow M. H. (2000) Functions of
-aspartylglutamate in the vertebrate brain. Role in glial cell-specific signaling.
Baslow M. H. (2000) Canavan’s spongiform leukodystrophy: A clinical anatomy of a genetic metabolic CNS disease. An analytical review.
J. Mol. Neurosci.
Baslow M. H., Suckow R. F., Berg M. J., Marks N., Saito M., and Bhakoo K. K. (2001) Differential expression of carnosine, homocarnosine and
-histidine hydrolytic activities in cultured rat macroglial cells.
J. Mol. Neurosci.
Baslow M. H. (2003)
-acetylaspartate in the vertebrate brain: Metabolism and function.
Baslow M. H. (2002) Evidence supporting a role for
-aspartate as a molecular water pump in myelinated neurons in the central nervous system. An analytical review.
Bahr B. A. (1995) Long-term hippocampal slices: A model system for investigating synaptic mechanisms and pathologic processes.
J. Neurosci. Res.
Bahr B. A., Kessler M., Rivera S., et al. (1995) Stable maintenance of glutamate receptors and other synaptic components in long-term hippocampal slices.
Bohme D. H. and Marks N. (1981) Myelin. p. 163–194, in
Advanced Cell Biology, Van Nostrand Reinhold Co., pp. 1175.
Brand A., Richter-Landsberg C., and Leibfritz D. (1997) Metabolism of acetate in rat brain neurons, astrocytes and cocultures: metabolic interactions between neurons and glia cells, monitored by NMR spectroscopy.
Cell. Mol. Biol.
Burlina A. P., Aureli T., Bracco F., Conti F., and Battistin L. (2000) MR spectroscopy: A powerful tool for investigating brain function and neurological diseases.
Duff K., Eckman C., Zehr C., Yu X., Prada C. M., Pereztur J., et al. (1996) Increased amyloid-beta 42(43) in brains of mice expressing mutant presenilin 1.
Florian C. -L., Williams S. R., Bhakoo K. K., and Noble M. D. (1996) Regional and developmental variations in metabolite concentration in the rat brain and eye: A study using
H NMR spectroscopy and high performance liquid chromatography.
Heun R., Schlegel S., Graf-Morgenstern M., Tintera J., Gawehn J., and Stoeter P. (1997) Proton magnetic resonance spectroscopy in dementia of Alzheimer type.
Int. J. Geriat. Psychiat.
Jenkins B. G., Klivenyi P., Kustermann E., Andreassen O. A., Ferrante R. J., Rosen B. R., and Beal M. F. (2000) Nonlinear decrease over time in
-acetyl aspartate levels in absence of neuronal loss and increases in glutamine and glucose in transgenic Huntington’s disease mice.
Martin E., Capone A., Schneider J., Hennig J., and Thiel T. (2001) Absence of
-acetylaspartate in the human brain: Impact on neurospectroscopy?
Moreno A., Ross B. D., and Bluml S. (2001) Direct determination of the
-aspartate synthesis rate in the human brain by
C MRS and [1-
C] glucose infusion.
Noraberg J. and Zimmer J. (1998) Ethanol induces MAP2 changes in organotypic hippocampal slice cultures.
Obst K. and Wahle P. (1995) Areal differences of NPY mRNA-expressing neurons are established in the late postnatal rat visual cortex in vivo, but not in organotypic cultures.
Eur. J. Neurosci.
Ostergaard K. (1993) Organotypic slice cultures of the rat striatum—I. A histochemical and immunocytochemical study of acetylcholinesterase, choline acetyltransferase, glutamate decarboxylase and GABA.
Schuff N., Amend D., Ezekiel F., et al. (1997) Changes in hippocampal
N-acetylaspartate and volume in Alzheimer’s disease. A proton MR spectroscopic imaging and MRI study. Neurol.
Simmons M. L., Frondoza C. G., and Coyle, J. T. (1999) Immunocytochemical localization of
-acetylaspartate with monoclonal antibodies.
Smith P. K., Krohn R. I., Hermanson G. T., et al. (1985) Measurement of protein using bicinchoninic acid.
Tsacopoulos M. and Magistretti P. J. (1996) Metabolic coupling between glia and neurons.