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The aging brain and changes in GABA concentrations

Lize Hermans1*, Inge Leunissen1, Celine Maes1, Stefanie Verstraelen2, Koen Cuypers1, 2, Richard A. Edden3, 4, Nicolaas A. Puts3, 4 and Stephan P. Swinnen1
  • 1 KU leuven, Department of Kinesiology, Belgium
  • 2 Hasselt University, Biomedical Research Institute, Belgium
  • 3 Kennedy Krieger Institute, United States
  • 4 the Johns Hopkins University School of Medicine, Department of Biomedical Engineering, United States

Introduction Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the human brain. Previous literature revealed a decline in GABA concentration in frontal and parietal regions as a result of age (Gao et al., 2013; Porges et al., 2017). Nevertheless, it is not clear whether this age-related decline in GABA concentration is specific to these regions or a widespread effect. Therefore, we aimed to investigate age-related changes in GABA concentrations within several cortical and subcortical regions. Since regional GABA concentration has been found to be correlated with various behavioral measures (Puts & Edden, 2012; Stagg, 2014), insight into the effect of healthy aging on brain chemistry may increase our understanding of the underlying neural mechanisms that contribute to cognitive and motor deficits in older adults. Methods A total of 30 healthy right-handed young (14 men, mean age = 23.2) and 29 healthy right-handed older adults (13 men, mean age = 67.5) participated in this study. GABA+ concentrations were acquired in nine different voxels using the MEGA-PRESS spectral editing method on a Philips 3T Achieva Magnetic Resonance scanner (Philips Healthcare, The Netherlands) with a 32 channel receiver head coil. The following acquisition parameters were used: 14 ms editing pulses at 7.5 ppm (edit-OFF) and 1.9 ppm (edit-ON), TE = 68 ms, TR = 2 s, 320 averages, 2 kHz spectral width, MOIST water suppression. Voxels of interest were bilateral primary motor cortex (3x3x3cm³), bilateral dorsal premotor cortex (4x2.5x2.5cm³), bilateral striatum (3x3x3cm³), presupplementary motor area (3x3x3cm³), right inferior frontal cortex (4x2.5x2.5cm³) and occipital cortex (3x3x3cm³). Additionally, a T1 scan was acquired in order to calculate the cerebrospinal fluid (CSF) fraction of each voxel. The obtained MRS spectra were analyzed using the Gannet software toolkit (Edden, Puts, Harris, Barker, & Evans, 2013) and GABA+ concentrations were calculated relative to water. Differences in GABA+ concentrations between young and older adults were tested with a mixed model with age group and voxel as fixed factor, participant as random factor and CSF as covariate (JMP Pro 12). Significant interaction effects were further investigated using unpaired student’s t-tests with Bonferroni correction. Results Older adults had lower GABA+ concentrations in all voxels in comparison with young adults (Figure 1). Statistical analysis however indicated that there was no effect of age on GABA+ concentrations (F1,106.4 = 0.317, p = .574), but there was an interaction between age and voxel (F8, 404.8 = 2.009, p = .0442). Between-group post hoc analysis showed lower GABA+ concentrations within right striatum in older adults compared to young adults (t = -2.86, p = .0045). GABA+ concentrations did not significantly differ between young and older adults in all other voxels (all p ≥ .1604). Conclusions In the present study, we found a decline in GABA+ concentrations with age, however, this decline was only present within right striatum. Within bilateral primary motor cortex, bilateral dorsal premotor cortex, left striatum, presupplementary motor area, right inferior frontal cortex and occipital cortex, the decline in GABA+ concentrations was not significant. This suggests that biochemical changes as a result of healthy aging are not uniform across the human brain. However, it is possible that the regional concentration of macromolecules (i.e. part of the edited GABA+ signal) changes as a function of age, thereby masking the decline in GABA concentrations.

Figure 1
Image

References

Edden, R. A. E., Puts, N. A. J., Harris, A. D., Barker, P. B., & Evans, C. J. (2013). Gannet: A batch-processing tool for the quantitative analysis of gamma-aminobutyric acid-edited MR spectroscopy spectra. Journal of Magnetic Resonance Imaging, 1452, 1445–1452.

Gao, F., Edden, R. A. E., Li, M., Puts, N. A. J., Wang, G., Liu, C., … Barker, P. B. (2013). Edited magnetic resonance spectroscopy detects an age-related decline in brain GABA levels. NeuroImage, 78, 75–82.

Porges, E. C., Woods, A. J., Edden, R. A. E., Puts, N. A. J., Harris, A. D., Chen, H., … Cohen, R. A. (2017). Frontal gamma-aminobutyric acid concentrations are associated with cognitive performance in older adults. Biological Psychiatry, 2(1), 38–44.

Puts, N. A. J., & Edden, R. A. E. (2012). In vivo magnetic resonance spectroscopy of GABA: A methodological review. Progress in Nuclear Magnetic Resonance Spectroscopy, 60, 29–41.

Stagg, C. J. (2014). Magnetic Resonance Spectroscopy as a tool to study the role of GABA in motor-cortical plasticity. NeuroImage, 86, 19–27.

Keywords: Aging, gamma-Aminobutyric Acid, Magnetic Resonance Spectroscopy, MEGA-PRESS, Striatum

Conference: 12th National Congress of the Belgian Society for Neuroscience, Gent, Belgium, 22 May - 22 May, 2017.

Presentation Type: Poster Presentation

Topic: Development

Citation: Hermans L, Leunissen I, Maes C, Verstraelen S, Cuypers K, Edden RA, Puts NA and Swinnen SP (2019). The aging brain and changes in GABA concentrations. Front. Neurosci. Conference Abstract: 12th National Congress of the Belgian Society for Neuroscience. doi: 10.3389/conf.fnins.2017.94.00028

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Received: 01 May 2017; Published Online: 25 Jan 2019.

* Correspondence: Ms. Lize Hermans, KU leuven, Department of Kinesiology, Leuven, 3001, Belgium, lize.hermans@kuleuven.be