Journal of Molecular Neuroscience

, Volume 32, Issue 3, pp 235–245

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
  • Morris H. Baslow
  • Jan Hrabe
  • David N. Guilfoyle
Article

DOI: 10.1007/s12031-007-0049-9

Cite this article as:
Baslow, M.H., Hrabe, J. & Guilfoyle, D.N. J Mol Neurosci (2007) 32: 235. doi:10.1007/s12031-007-0049-9

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.

Keywords

N-AcetylaspartateN-acetylaspartylglutamateMagnetic resonance spectroscopyFunctional MRSMolecular water pumpOsmoregulation

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

Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  • Morris H. Baslow
    • 1
  • Jan Hrabe
    • 2
  • David N. Guilfoyle
    • 2
  1. 1.Center for NeurochemistryNathan S. Kline Institute for Psychiatric ResearchOrangeburgUSA
  2. 2.Center for Advanced Brain ImagingNathan S. Kline Institute for Psychiatric ResearchOrangeburgUSA