Investigation into the Role of N‐Acetylaspartate in Cerebral Osmoregulation

Abstract

Marked abnormalities of the magnetic resonance intensity of N‐acetylaspartate (NAA) have been reported in patients with various neurological disorders, but the neurochemical consequences of these alterations are difficult to assess because the function of NAA remains speculative. The purpose of this study was to examine whether NAA plays a role in protecting neurons against osmotic stress. Intracerebral microdialysis was used to expose a small region of the rat dorsolateral striatum to an increasingly hyposmotic environment and to measure resulting changes in NAA extracellular concentrations. NAA changes in the extracellular fluid (ECF) were compared with those of the amino acids, in particular, taurine, known to be involved in brain osmoregulation. Stepped increases in cellular hydration produced by hyposmotic perfusion media induced a marked increase in ECF NAA, reflecting a redistribution of NAA from intra‐to extracellular space. Parallel experiments showed that, of all the extracellular amino acids measured, only taurine markedly increased with hyposmolar perfusion medium, indicating that the ECF NAA increase associated with hyposmotic stress was a specific response and not passive leakage out of the cells. As NAA is predominantly neuronal, it may contribute to the protection of neurons against swelling (i.e., regulatory volume decrease). In conditions with impaired blood‐brain barrier and cytotoxic oedema, efflux of intracellular NAA subsequent to sustained cellular swelling might lead to a reduction in total brain NAA detectable by magnetic resonance spectroscopy. Alternatively, redistribution of NAA from intra‐to extracellular space implies changes in its chemical environment that may alter its magnetic resonance visibility.

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

“…In the 1990's, Taylor and colleagues proposed that NAA acted as a neuronal osmolyte involved in either neuronal volume regulation, or acid-base homeostasis. (Taylor et al, 1994) Using microdialysis, they demonstrated that NAA concentrations in the extracellular fluid increased in response to hypoosmotic stress (Taylor et al, 1995). Despite this, the changes in extracellular NAA concentrations were relatively modest (from ~14 μM to ~32 μM) as compared with the substantially larger increases in extracellular taurine concentrations (from ~ 12 μM to ~ 80 μM) under the same hypoosmotic conditions.…”

“…First, these investigators observed much larger changes in NAA in response to hypo-osmotic stress than were seen with taurine. Microdialysis studies have shown that taurine concentrations respond more to osmotic changes than have been observed with NAA (Taylor et al, 1995). Second, such large decreases in NAA levels after hypo-osmotic stress have not been observed using other methods (Verbalis, 2006).…”

Effects of short-term dietary nitrate supplementation on blood pressure, O2uptake kinetics, and muscle and cognitive function in older adults

“…NAA has been shown to be closely related to mitochondrial activity in ATP production and O 2 consumption (6), which suggests an association between [NAA] and metabolic efficiency in the brain (73). Previous studies have shown that [NAA] is associated with both intellectual and neuropsychological (84) measures of cognition in young adults.…”

Feeding versus infusion: a novel approach to study the NAA metabolism in rat brain

“…1 Despite its high cerebral concentration, however, the functional role of NAA is not yet established beyond doubt, although some studies suggest that NAA could play a role in osmoregulation 2 or as an intermediate for the synthesis of proteins and lipids. 3 As its synthesis and degradation take place in different compartments, it has been suggested that NAA might play a role in the neuronal-glial cell-specific signaling and communication in the development of normal central nervous system.…”