Inhibition of N-acetylaspartate production

The Relationship between Dorsolateral Prefrontal Neuronal N-Acetylaspartate and Evoked Release of Striatal Dopamine in Schizophrenia

“…While the biological role of NAA has yet to be clearly defined, it acts via the glutamatergic NMDA receptor to elevate intracellular calcium (Rubin et al 1995), and its concentrations are reduced by pharmacological inhibition of mitochondrial energy metabolism (Bates et al 1996) as well as by a number of pathological processes affecting the integrity of neurons (Cendes et al 1997;De Stefano et al 1995;Najim et al 1998). Other data also suggest that NAA concentrations vary with the structural and functional state of glutamatergic cells.…”

Dysregulation of dopamine and pathology of prefrontal neurons: neuroimaging studies in schizophrenia and related animal models

“…NAA synthesis takes place in the mitochondria, it is ADP dependent and uses glutamate as a precursor (Bates et al, 1996). While the biological role of NAA has yet to be clearly defined, it acts via the glutamatergic NMDA receptor to elevate intracellular calcium (Rubin et al, 1995); its concentrations are reduced by pharmacological inhibition of mitochondrial energy metabolism; its reductions correlate highly with the relative reduction of ATP and O 2 consumption (Bates et al, 1996). Moreover, a number of studies have demonstrated that NAA reductions are reversible suggesting that NAA is sensitive to pathological processes affecting the function of neurons (Clark, 1998).…”

N-acetylaspartate Decrease in Acute Stage of Ischemic Stroke:A Perspective from Experimental and Clinical Studies

“…27 Finally, NAA is synthesized by membrane-bound L-aspartate Nacetyltransferase (Asp-NAT) 28 in an energy-dependent manner. 6,12,29 Partly because of that energy dependence and the involvement of the TCA cycle in the conversion of malate to aspartate in mitochondria, NAA biosynthesis is very susceptible to energy failure. 6 Once synthesized, NAA is transported to the cytosol by the dicarboxylic acid transporter.…”

“…6,12,29 Partly because of that energy dependence and the involvement of the TCA cycle in the conversion of malate to aspartate in mitochondria, NAA biosynthesis is very susceptible to energy failure. 6 Once synthesized, NAA is transported to the cytosol by the dicarboxylic acid transporter. 30 A recent report identified the synthesis of a small but distinct amount of NAA in cytosol.…”

“…Lactate appears within minutes of the occlusion due to an acceleration of anaerobic glycolysis, which compensates for hampered mitochondrial oxidation. Because NAA synthesis is adenosine triphosphate (ATP)-dependent (energydependent), 6 impaired energy availability initiates a continuous decline in levels of NAA, the rate of which depends in part on severity, within hours of the ischemic event. Although magnetic resonance (MR) imaging, especially diffusion-weighted images (DWI) and perfusion images (PI), is a powerful technique for visualizing pathological changes in vivo that can be applied to ischemic stroke, we believe observation of biomarkers that directly reflect metabolic changes during the acute stage will be highly valuable for making the most appropriate therapeutic decisions.…”