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Dynamic Relationship Between Neurostimulation and N-Acetylaspartate Metabolism in the Human Visual Cortex

Evidence that NAA functions as a molecular water pump during visual stimulation

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Abstract

N-acetyl-l-aspartic acid (NAA), an amino acid synthesized and stored primarily in neurons in the brain, has been proposed to be a molecular water pump (MWP) whose function is to rapidly remove water from neurons against a water gradient. In this communication, we describe the results of a functional 1H proton magnetic resonance spectroscopy (fMRS) study, and provide evidence that in the human visual cortex, over a 10-min period of visual stimulation, there are stimulation-induced graded changes in the NAA MRS signal from that of a preceding 10-min baseline period with a decline in the NAA signal of 13.1% by the end of the 10-min stimulation period. Upon cessation of visual stimulation, the NAA signal gradually increases during a 10-min recovery period and once again approaches the baseline level. Because the NAA MRS signal reflects the NAA concentration, these changes indicate rapid focal changes in its concentration, and transient changes in its intercompartmental metabolism. These include its rates of synthesis and efflux from neurons and its hydrolysis by oligodendrocytes. During stimulation, the apparent rate of NAA efflux and hydrolysis increased 14.2 times, from 0.55 to 7.8 μmol g−1 h−1. During recovery, the apparent rate of synthesis increased 13.3 times, from 0.55 to 7.3 μmol g−1 h−1. The decline in the NAA signal during stimulation suggests that a rapid increase in the rate of NAA-obligated water release to extracellular fluid (ECF) is the initial and seminal event in response to neurostimulation. It is concluded that the NAA metabolic cycle in the visual cortex is intimately linked to rates of neuronal signaling, and that the functional cycle of NAA is associated with its release to ECF, thus supporting the hypothesis that an important function of the NAA metabolic cycle is that of an efflux MWP.

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Abbreviations

Ac:

acetate

AcCoA:

acetyl-coenzyme A

Asp:

aspartic acid

ATP:

adenosine triphosphate

AQP4:

aquaporin 4

BOLD:

blood oxygen level-dependent imaging

CI:

confidence interval

ECF:

extracellular fluid

ECS:

extracellular space

fMRS:

functional magnetic resonance spectroscopy

Glc:

glucose

GLUT 1:

Glc transporter 1

1H MRS:

proton magnetic resonance spectroscopy

MRS:

magnetic resonance spectroscopy

NAA:

N-acetyl-l-aspartic acid

NAAG:

N-acetylaspartylglutamic acid

NMR:

nuclear magnetic resonance

tNAA:

total NAA + NAAG

ROI:

region of interest

SNR:

signal to noise ratio

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Acknowledgement

This study was supported in part by a grant from the National Institutes of Health, National Institute of Biomedical Imaging and Bioengineering (1 R21 EB004727-01).

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Authors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY, 10962, USA

    Morris H. Baslow

  2. Center for Advanced Brain Imaging, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY, 10962, USA

    Jan Hrabe & David N. Guilfoyle

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  1. Morris H. Baslow
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  2. Jan Hrabe
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  3. David N. Guilfoyle
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Correspondence to Morris H. Baslow.

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Baslow, M.H., Hrabe, J. & Guilfoyle, D.N. Dynamic Relationship Between Neurostimulation and N-Acetylaspartate Metabolism in the Human Visual Cortex. J Mol Neurosci 32, 235–245 (2007). https://doi.org/10.1007/s12031-007-0049-9

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