N-Acetyl-Aspartate (NAA) Metabolism

Bhakoo, Kishore

doi:10.1007/978-1-4614-1788-0_38

Cited by 5 publications

(4 citation statements)

References 144 publications

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“…In addition, all of the above interpretations of NAA levels solely base on the putative role of NAA as a marker for the density of healthy neurons, but NAA levels may also reflect mitochondrial activity, osmolytic balance and has other putative roles, which led K.K. Bhakoo recently to conclude in his review on NAA metabolism that "… its function/s remains an enigma" [50].…”

Section: Discussionmentioning

confidence: 99%

Magnetic resonance spectroscopy investigations of functionally defined language areas in schizophrenia patients with and without auditory hallucinations

et al. 2014

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Background: Cerebral dysfunction occurring in mental disorders can show metabolic disturbances which are limited to circumscribed brain areas. Auditory hallucinations have been shown to be related to defined cortical areas linked to specific language functions. Here, we investigated if the study of metabolic changes in auditory hallucinations requires a functional rather than an anatomical definition of their location and size to allow a reliable investigation by magnetic resonance spectroscopy (MRS). Methods: Schizophrenia patients with (AH; n=12) and without hallucinations (NH; n=8) and healthy controls (HC; n=11) underwent a verbal fluency task in functional MRI (fMRI) to functionally define Broca's and Wernicke's areas. Left and right Heschl's gyrus were defined anatomically. Results: The mean distances in native space between the fMRI-defined regions and a corresponding anatomically defined area were 12.4±6.1 mm (range: 2.7-36.1 mm) for Broca's area and 16.8±6.2 mm (range:4.5-26.4 mm) for Wernicke's area, respectively. Hence, the spatial variance was of similar extent as the size of the investigated regions. Splitting the investigations into a single voxel examination in the frontal brain and a spectroscopic imaging part for the more homogeneous field areas led to good spectral quality for almost all spectra. In Broca's area, there was a significant group effect (p = 0.03) with lower levels of N-acetyl-aspartate (NAA) in NH compared to HC (p = 0.02). There were positive associations of NAA levels in the left Heschl's gyrus with total (p = 0.03) and negative (p = 0.006) PANSS scores. In Broca's area, there was a negative association of myo-inositol levels with total PANSS scores (p = 0.008). Conclusion: This study supports the neurodegenerative hypothesis of schizophrenia only in a frontal region whereas the results obtained from temporal regions are in contrast to the majority of previous studies. Future research should test the hypothesis raised by this study that a functional definition of language regions is needed if neurochemical imbalances are expected to be restricted to functional foci. Highlights

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Section: Discussionmentioning

confidence: 99%

Magnetic resonance spectroscopy investigations of functionally defined language areas in schizophrenia patients with and without auditory hallucinations

et al. 2014

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“…The mechanisms of lipid synthesis and energy production in the brain are very peculiar. Numerous metabolites participate in brain lipid metabolism, including NAA, which is synthesized from l -aspartate and acetyl-coenzyme A in neurons. − During postnatal central nervous system development, the expression of lipogenic enzymes, such as the NAA-degrading enzyme aspartoacylase (ASPA), increase in oligodendrocytes along with the production of NAA in neurons. ,, Interestingly, our metabolomic analysis showed evidence that the lack of d -Asp is linked to an increment of NAA in R26 d do / d do mouse tissues at E13.5 and P3 compared to R26 +/+ mice. Besides lipids, other metabolites involved in brain energetic processes have been identified by VIP analysis in R26 d do / d do brain tissues, such as oxaloacetate, glucose, lactate, and malate, directly involved in the Krebs cycle (see Supporting Information Figure S2).…”

Section: Discussionmentioning

confidence: 82%

“…Numerous metabolites participate in brain lipid metabolism, including NAA, which is synthesized from L-aspartate and acetyl-coenzyme A in neurons. 62−66 During postnatal central nervous system development, the expression of lipogenic enzymes, such as the NAA-degrading enzyme aspartoacylase (ASPA), 67 increase in oligodendrocytes along with the production of NAA in neurons. 62,68,69 Interestingly, our metabolomic analysis showed evidence that the lack of D-Asp is linked to an increment of NAA in R26 Ddo/Ddo mouse tissues at E13.5 and P3 compared to R26 +/+ mice.…”

Section: ■ Discussionmentioning

confidence: 99%

Prenatal and Early Postnatal Cerebral d-Aspartate Depletion Influences l-Amino Acid Pathways, Bioenergetic processes, and Developmental Brain Metabolism

et al. 2020

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D-Amino acids were believed to occur only in bacteria and invertebrates. Today, it is well known that D-amino acids are also present in mammalian tissues in a considerable amount. In particular, high levels of free D-serine (D-Ser) and Daspartate (D-Asp) are found in the brain. While the functions of D-Ser are well known, many questions remain unanswered regarding the role of D-Asp in the central nervous system. D-Asp is very abundant at the embryonic stage, while it strongly decreases after birth because of the expression of D-aspartate oxidase (Ddo) enzyme, which catalyzes the oxidation of this D-amino acid into oxaloacetate, ammonium, and hydrogen peroxide. Pharmacologically, D-Asp acts as an endogenous agonist of N-methyl D-aspartate and mGlu5 receptors, which are known to control fundamental brain processes, including brain development, synaptic plasticity, and cognition. In this work, we studied a recently generated knockin mouse model (R26 Ddo/Ddo ), which was designed to express DDO beginning at the zygotic stage. This strategy enables D-Asp to be almost eliminated in both prenatal and postnatal lives. To understand which biochemical pathways are affected by depletion of D-Asp, in this study, we carried out a metabolomic and lipidomic study of Ddo knockin brains at different stages of embryonic and postnatal development, combining nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS) techniques.Our study shows that D-Asp deficiency in the brain influences amino acid pathways such as threonine, glycine, alanine, valine, and glutamate. Interestingly, D-Asp is also correlated with metabolites involved in brain development and functions such as choline, creatine, phosphocholine (PCho), glycerophosphocholine (GPCho), sphingolipids, and glycerophospholipids, as well as metabolites involved in brain energy metabolism, such as GPCho, glucose, and lactate.

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“…This would suggest that LAC effects on these metabolites may be secondary and part of a slower process. Nevertheless, as NAA, Glu and Asp measured with MRS reflect mainly neuronal metabolism (84, 85), we can hypothesize that astrocytes are the first beneficiary of LAC supplementation. Astrocytes are indeed specifically shaped to uptake blood fatty acids, ketone bodies and acetate, and presumably acetyl-L-carnitine (86–88).…”

Section: Discussionmentioning

confidence: 96%

Metabolic signature in nucleus accumbens for anti-depressant-like effects of acetyl-L-carnitine: Anin vivo¹H-magnetic resonance spectroscopy study at 14 T

Cherix

Larrieu²,

Grosse

et al. 2019

Preprint

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BackgroundEmerging evidence suggests that hierarchical status may provide vulnerability to develop stress-induced depression. Energy metabolism in the nucleus accumbens (NAc) was recently related to hierarchical status and vulnerability to develop depression-like behavior. Acetyl-L-carnitine (LAC), a mitochondria-boosting supplement, has shown promising antidepressant-like effects opening promising therapeutic strategies for restoring energy balance in depressed patients. Here, we investigated the metabolic impact in the NAc of antidepressant LAC treatment in chronically stressed mice.MethodMice were characterized for emotional behaviors and social rank. They were then exposed to chronic restraint stress (CRS) for 21 days and subsequently tested in a social behavior (SB) test. A group of mice was also given LAC supplementation during the 7 last CRS days. Mice were then tested in the SB and forced swim tests (FST) and scanned in vivo using 1H-magnetic resonance spectroscopy (1H-MRS) to quantitatively assess the NAc neurochemical profile.ResultsDominant, but not subordinate, mice showed behavioral vulnerability to CRS. In the NAc, dominant mice showed reduced levels of several energy-related metabolites. LAC treatment counteracted stress-induced behavioral changes in dominant mice, and normalized levels of taurine, phosphocreatine, glutamine and phosphocholine in the NAc. No major accumbal metabolic changes were observed in subordinate mice.ConclusionHigh social rank is confirmed as a vulnerability factor to develop chronic stress-induced depressive-like behaviors. We reveal a metabolic signature in the NAc for the antidepressant-like effects of LAC in vulnerable mice, characterized by restoration of stress-induced alterations in neuroenergetics and lipid function.

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N-Acetyl-Aspartate (NAA) Metabolism

Cited by 5 publications

References 144 publications

Magnetic resonance spectroscopy investigations of functionally defined language areas in schizophrenia patients with and without auditory hallucinations

Magnetic resonance spectroscopy investigations of functionally defined language areas in schizophrenia patients with and without auditory hallucinations

Prenatal and Early Postnatal Cerebral d-Aspartate Depletion Influences l-Amino Acid Pathways, Bioenergetic processes, and Developmental Brain Metabolism

Metabolic signature in nucleus accumbens for anti-depressant-like effects of acetyl-L-carnitine: Anin vivo¹H-magnetic resonance spectroscopy study at 14 T

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N-Acetyl-Aspartate (NAA) Metabolism

Cited by 5 publications

References 144 publications

Magnetic resonance spectroscopy investigations of functionally defined language areas in schizophrenia patients with and without auditory hallucinations

Magnetic resonance spectroscopy investigations of functionally defined language areas in schizophrenia patients with and without auditory hallucinations

Prenatal and Early Postnatal Cerebral d-Aspartate Depletion Influences l-Amino Acid Pathways, Bioenergetic processes, and Developmental Brain Metabolism

Metabolic signature in nucleus accumbens for anti-depressant-like effects of acetyl-L-carnitine: Anin vivo1H-magnetic resonance spectroscopy study at 14 T

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Metabolic signature in nucleus accumbens for anti-depressant-like effects of acetyl-L-carnitine: Anin vivo¹H-magnetic resonance spectroscopy study at 14 T