Introduction

W-Acetylaspartylglutamate (NAAG), the most abundant brain peptide,1 has been localized immunocytochemically in a variety of neurons throughout the nervous system. In many cases, NAAG's presence has been confirmed by HPLC, but these results will not be described here. NAAG is also sometimes found in glia,2, 3 which are partially responsible for its synthesis.4 In neurons, NAAG is seen in the cytoplasm around the nucleus, in proximal dendrites, and in axons and terminals, including synaptic...

Traumatic Brain Injury

TBI is the leading cause of death and morbidity in young, otherwise healthy young adults and children. Due to variability in the form and extent of the initial injury, as well as individual variation in response to injuries, prediction of outcome following TBI is challenging and generally inadequate 16 . Common clinical markers, such as the Glasgow Coma Scale (GCS) are linked statistically with outcome in large samples, but are less useful in predicting cognitive functioning in individual...

Conclusions

The active transport of N-acetyl-L-aspartate in astrocytes is mediated by NaC3, a Na+-coupled transporter belonging to the SLC13 gene family. Since the uptake of N-acetyl-L-aspartate into glial cells is a prerequisite for intracellular hydrolysis of this compound by aspartoacyalse II, a process involved in the utilization of N-acetyl-L-aspartate in myelination, we speculate that functional defects in NaC3 may lead to defective myelination. The SLC13A3 gene coding for human NaC3 is located on...

Conclusion And Future Directions

MRS can provide important insights into the regional chemical pathology of the brain and how this chemical pathology changes in response to drug therapy. As an index of neuronal integrity, NAA holds promise as a biomarker of degeneration and a surrogate marker of therapeutic efficacy in ALS. NAA changes in the brain parallel the spatial distribution of pathologic changes and modest associations are present with clinical parameters. However, to date, the finding of reduced motor cortex NAA lacks...

Wacetylaspartylglutamate Naag

Several laboratories have studied the cellular localization of NAAG in the brains of a number of species using immunocytochemical methods. The immunogen has routinely been NAAG linked by to a carrier protein by carbodiimide. To minimize cross-reacticity with NAA, polyclonal antibodies purified by affinity chromatography, 13'14 or a highly specific monoclonal antibody has been selected.15 Consistent with the uneven regional distribution of NAAG levels, NAAG expression is restricted to discrete...

Adult

Evolution of aspartoacylase activity (specific activity, jM min mg protein) - mean + S.D. n 4) in the optic nerve during postnatal development. A differential distribution of aspartoacylase activity between gray and white matter has been has been demonstrated in previous studies. The study by D'Adamo et al.36 on the occurrence of aspartoacylase activity in the developing rat brain showed an approximately three-fold difference between white and gray matter in the adult cerebral...

Normal Adults

Several studies from different laboratories have now reported that greater NAA is associated with better performance on some type of cognitive test, particularly broad measures of cognitive functioning such as those found in measures of intellectual functioning 2 . The details vary, as different brains regions have been studied with diverse tests, but the general finding seems fairly well established in vivo measures of NAA are positively correlated with cognitive performance in normal...

Conclusion

In closing, it is anticipated that this conference will not only provide a comprehensive review of the current state of knowledge of NAA and NAAG but will also define the many important and critical questions that need to be addressed in future research. It is hoped that the proceedings of the conference will attract a broader interest in these moieties, as they have been linked to serious disorders including schizophrenia, Alzheimer's Disease and pain. Given their remarkably high...

NAA Toxicity in Canavan Disease

An additional controversy concerning NAA is that it is toxic to neurons when the concentration is substantially elevated in the brain, as in the case of many Canavan disease patients.29 Canavan disease (CD) is a fatal, hereditary leukodystrophy that compromises myelination in the CNS. CD is caused by mutations in the gene for ASPA,30,31 an enzyme that currently is thought to function exclusively to hydrolyze NAA into L-aspartate and free acetate. However, ASPA is strongly expressed in other...

Activitydependent Regulation Of Naag Expression

I examined NAAG immunoreactivity in the retina and LGN of monocularly deprived (MD) cats and compared it with that in normal cats.51, 52 As noted above, in the LGN of the normal cat, both the neuropil and the somata of relay cells are heavily labeled. Long-term monocular deprivation decreases labeling of the somata, but not the neuropil, in the deprived layers of the LGN (Fig. 5). There is little or no loss of label in the retinal ganglion cells of the deprived eye, as might be expected, given...

NAAG in Groups with Known Neurotransmitters

NAAG is strongly expressed in several neuronal groups known to utilize specific neurotransmitters. Examples include the vertical limb of the diagonal band of Broca, which is known to use acetylcholine as the primary neurotransmitter (Figure 9A). The locus coeruleus is a noradrenergic nucleus in the brainstem which is strongly immunoreactive for NAAG (Figure 9B), and the substantia niagra pars compacta is a major dopaminergic nucleus in the midbrain which expresses high levels of NAAG-IR (Figure...

Naa Naag and Aspartoacylase Expression in Corpus Callosum

Aspartoacylase is an enzyme that specifically de-acetylates NAA, and which was observed almost exclusively in oligodendrocytes Figure 5A . In contrast, NAA and NAAG were expressed primarily in neurons Figures 5B, C . Aspartoacylase-stained cells were arranged in characteristic rows between axon bundles in the corpus callosum. Low levels of NAA can also be seen in rows of oligodendrocytes. The level of NAA-IR in adult rat oligodendrocytes is substantially lower than the level in neurons. NAAG is...

Hyperosmolality

Hyperosmolality and hypernatremia usually occurs as a result of hypotonic fluid losses that are not compensated by sufficient water intake to maintain body fluid homeostasis. Less commonly, excess NaCl ingestion or administration can cause hyperosmolality as a result of solute excess. Although hyperosmolality can develop in association with a broad spectrum of disease processes in people of all ages, infants and elderly individuals are particularly susceptible 4 . The neurological symptoms of...

References

Verbalis JG, The syndrome of inappropriate antidiuretic hormone secretion and other hypoosmolar disorders. In Schrier RW ed . Diseases of the Kidney and Urinary Tract.Lippincott Williams amp Wilkins, Philadelphia 2511-2548, 2001 . 2. Gullans SR, Verbalis JG, Control of brain volume during hyperosmolar and hypoosmolar conditions. Annual Review of Medicine 44, 289-301, 1993 . 3. Verbalis JG, Adaptation to acute and chronic hyponatremia implications for symptomatology, diagnosis, and therapy....