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. 2021 Jan 12;11(1):722.
doi: 10.1038/s41598-020-80530-8.

Macromolecule suppressed GABA levels show no relationship with age in a pediatric sample

Tiffany Bell  1   2   3 , Mehak Stokoe  4   5   6 , Ashley D Harris  4   5   6
Affiliations

Macromolecule suppressed GABA levels show no relationship with age in a pediatric sample

Tiffany Bell et al. Sci Rep. .

Abstract

The inhibitory neurotransmitter γ-Aminobutyric acid (GABA) plays a crucial role in cortical development. Therefore, characterizing changes in GABA levels during development has important implications for the study of healthy development and developmental disorders. Brain GABA levels can be measured non-invasively using GABA-edited magnetic resonance spectroscopy (MRS). However, the most commonly used editing technique to measure GABA results in contamination of the GABA signal with macromolecules (MM). Therefore, GABA measured using this technique is often referred to as GABA+ . While few in number, previous studies have shown GABA+ levels increase with age during development. However, these studies are unable to specify whether it is specifically GABA that is increasing or, instead, if levels of MM increase. In this study, we use a GABA-editing technique specifically designed to suppress the MM signal (MM-supp GABA). We find no relationship between MM-supp GABA and age in healthy children aged 7-14 years. These findings suggest that the relationship between GABA+ and age is driven by changes in MM levels, not by changes in GABA levels. Moreover, these findings highlight the importance of accounting for MM levels in MRS quantification.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Example voxel placement and spectra from all participants from (a) Thalamus, (b) Sensorimotor cortex and (c) Occipital cortex.
Figure 2
Figure 2
Regional differences in MM-Supp GABA levels and GM ratio. (a) MM-supp GABA. (b) MM-supp GABA (α-corrected). (c) MM-supp GABA/Cr. (d) GM ratio. Lines represent mean ± standard deviation. **p < 0.01, ***p < 0.001.
Figure 3
Figure 3
Correlations between the three versions of MM-supp GABA levels and age. (a) Correlation between MM-supp GABA and age. (b) Correlation between α-corrected MM-supp GABA and age. (c) Correlation between MM-supp GABA/Cr and age. TH: Thalamus (red); SM: Sensorimotor cortex (green); OC: Occipital cortex (blue).
Figure 4
Figure 4
Correlation between GM ratio (fGM/[fGM + fWM]) and age. TH: Thalamus (red); SM: Sensorimotor cortex (green); OC: Occipital cortex (blue).
See this image and copyright information in PMC

References

    1. Rae CD. A guide to the metabolic pathways and function of metabolites observed in human brain 1H magnetic resonance spectra. Neurochem. Res. 2014;39:1–36. doi: 10.1007/s11064-013-1199-5. - DOI - PubMed
    1. Wu X, et al. GABA signaling promotes synapse elimination and axon pruning in developing cortical inhibitory interneurons. J. Neurosci. 2012;32:331–343. doi: 10.1523/JNEUROSCI.3189-11.2012. - DOI - PMC - PubMed
    1. Mescher M, Merkle H, Kirsch J, Garwood M, Gruetter R. Simultaneous in vivo spectral editing and water suppression. NMR Biomed. 1998;11:266–272. doi: 10.1002/(SICI)1099-1492(199810)11:6<266::AID-NBM530>3.0.CO;2-J. - DOI - PubMed
    1. Harris AD, Puts NAJ, Barker PB, Edden RAE. Spectral-editing measurements of GABA in the human brain with and without macromolecule suppression. Magn. Reson. Med. 2015;74:1523–1529. doi: 10.1002/mrm.25549. - DOI - PMC - PubMed
    1. Harris AD, Saleh MG, Edden RAE. Edited 1H magnetic resonance spectroscopy in vivo: Methods and metabolites. Magn. Reson. Med. 2017;77:1377–1389. doi: 10.1002/mrm.26619. - DOI - PMC - PubMed

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