An answer to "The Nagging Question of the Function of N-Acetylaspartylglutamate"

Baslow, Morris H.

doi:10.14800/nc.844

Cited by 4 publications

(2 citation statements)

References 23 publications

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“…In addition, NAAG may account for some of the observed increase in tNAA, and could mark metabolic activity and availability for synthesis of glutamate (Rae, 2014). Baslow (2015) proposed a role of NAAG metabolism in complex task performance, so NAAG may increase as children engage in more cognitively demanding tasks (e.g., reading, math). This is especially relevant in the two regions investigated here, which are involved in executive functioning and language/reading processes that develop throughout childhood (Braver et al, 2021;Numssen et al, 2021;Richlan, 2012).…”

Section: Discussionmentioning

confidence: 99%

Changes in brain metabolite levels across childhood

Perdue

DeMayo

Bell

et al. 2022

Preprint

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Metabolites play important roles in brain development and their levels change rapidly in in the prenatal period and during infancy. Metabolite levels are thought to stabilize during childhood, but the development of neurochemistry across early-middle childhood remains understudied. We examined the developmental changes of key metabolites (total N- acetylaspartate, tNAA; total choline, tCho; total creatine, tCr; glutamate+glutamine, Glx; and myo-inositol, mI) using short echo-time magnetic resonance spectroscopy (MRS) in the anterior cingulate cortex (ACC) and the left temporo-parietal cortex (LTP) using a mixed cross- sectional/longitudinal design in children aged 2-11 years (ACC: N=101 children, 112 observations; LTP: N=95 children, 318 observations). We found age-related effects for all metabolites. tNAA increased with age in both regions, while tCho decreased with age in both regions. tCr increased with age in the LTP only, and mI decreased with age in the ACC only. Glx did not show linear age effects in either region, but a follow-up analysis in only participants with ≥3 datapoints in the LTP revealed a quadratic effect of age following an inverted U-shape. These substantial changes in neurochemistry throughout childhood likely underlie various processes of structural and functional brain development.

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Section: Discussionmentioning

confidence: 99%

Changes in brain metabolite levels across childhood

Perdue

DeMayo

Bell

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…At the same time, two papers were published, one that demonstrated for the first time that the enzyme that hydrolyzed NAA was only expressed in oligodendrocytes [4], and the other that showed that the enzyme that hydrolyzed NAAG was expressed "exclusively in astrocytic glial cells" [5]. The "nagging" question of the function of NAAG was considered in 1997 [6] and revisited in 2015 [7].…”

Section: Introductionmentioning

confidence: 99%

Evidence that N-acetyaspartylglutamate is the astrocyte-targeted neurovascular coupling agent that regulates slow tonic control of brain blood flow

Baslow

Guilfoyle

2016

JGM

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N-acetylaspartylglutamate (NAAG) is the highest concentration dipeptide present in brain. It is found primarily in neurons but its function is unclear. NAAG is synthesized by neurons from N-acetylaspartate and glutamate (Glu), maintained at mM concentrations and is released non-synaptically to extracellular fluid (ECF). NAAG is a non-excitatory form of Glu, and is targeted to the metabotropic group II Glu receptor 3 (mGluR3) on the surface of astrocytes. After docking with the receptor, Glu is released by the action of NAAG peptidase.Previously, it was shown for the first time that an NAAG-peptidase inhibitor reduced global cerebral blood flow (CBF) in mouse brain but did not affect their physical performance. Recently, it has been demonstrated that there are two separate systems involved in neurovascular coupling by astrocytes, one is a rapid focal phasic response providing energy for stimulation-induced neuronal activity, and the other a slower global tonic response providing energy for ongoing metabolic activities. Many neurovascular coupling mechanisms are known that regulate phasic changes in CBF, but how the brain accomplishes tonic control is unknown. In this paper we bring together two separate lines of inquiry, the decades' long search for the function of NAAG, and the more recent search for the mechanism of tonic neurovascular control. Herein, we present evidence that NAAG is the neurovascular coupling agent that regulates tonic changes in CBF via the astrocyte mGluR3-NAAG peptidase connection.

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1H MRS spectroscopy in preclinical autosomal dominant Alzheimer disease

Medina

Ringman

O’Neill

2018

Brain Imaging and Behavior

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H magnetic resonance spectroscopy (MRS) can reveal changes in brain biochemistry in vivo in humans and has been applied to late onset Alzheimer disease (AD). Carriers of mutations for autosomal dominant Alzheimer disease (ADAD) may show changes in levels of metabolites prior to the onset of clinical symptoms. Proton MR spectra were acquired at 1.5 T for 16 cognitively asymptomatic or mildly symptomatic mutation carriers (CDR < 1) and 11 non-carriers as part of a comprehensive cross-sectional study of preclinical ADAD. Levels of N-acetyl-aspartate+N-acetyl-aspartyl-glutamate (NAA), glutamate/glutamine (Glx), creatine/phosphocreate (Cr), choline (Cho), and myo-inositol (mI) in the left and right anterior cingulate and midline posterior cingulate and precuneus were compared between mutation carriers (MCs) and non-carriers (NCs) using multivariate analysis of variance with age as a covariate. Among MCs, correlations between metabolite levels and time until expected age of dementia diagnosis were calculated. MCs had significantly lower levels of NAA and Glx in the left pregenual anterior cingulate cortex, and lower levels of NAA and higher levels of mI and Cho in the precuneus compared to NCs. Increased levels of mI were seen in these regions in association with increased proximity to expected age of dementia onset. MRS shows effects of ADAD similar to those seen in late onset AD even during the preclinical period including lower levels of NAA and higher levels of mI. These indices of neuronal and glial dysfunction might serve as surrogate outcome measures in prevention studies of putative disease-modifying agents.

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An answer to "The Nagging Question of the Function of N-Acetylaspartylglutamate"

Cited by 4 publications

References 23 publications

Changes in brain metabolite levels across childhood

Changes in brain metabolite levels across childhood

Evidence that N-acetyaspartylglutamate is the astrocyte-targeted neurovascular coupling agent that regulates slow tonic control of brain blood flow

1H MRS spectroscopy in preclinical autosomal dominant Alzheimer disease

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