The relationship between measurement of in vivo brain glutamate and markers of iron metabolism: A proton magnetic resonance spectroscopy study in healthy adults

• Published in: The European journal of neuroscience 2020-02, Vol.51 (4), p.984-990
• Main Authors: Burger, Antoinette, Kotze, Maritha J., Stein, Dan J., Janse van Rensburg, Susan, Howells, Fleur M.
• Format: Article
• Language: English
• Subjects: anterior cingulate cortex; Copper; Cortex (frontal); Creatine; dorsolateral prefrontal cortex area; frontal white matter; glutamate with glutamine in relation to creatine containing metabolites; Glutamine; Iron; Magnetic resonance spectroscopy; Metabolism; Metabolites; Molecular modelling; Neuroimaging; Prefrontal cortex; Sex; Sex differences; Spectrum analysis; Substantia alba; transferrin; Transferrins
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/ejn.14583

Fundamental human studies which address associations between glutamate and iron metabolism are needed. Basic research reports associations between glutamate and iron metabolism. Human studies report sex differences in iron metabolism and glutamate concentrations, which suggest that these relationships may differ by sex. We hypothesised associations would be apparent between in vivo glutamate and peripheral markers of iron metabolism, and these associations would differ by sex. To test this, we recruited 40 healthy adults (20 men, 20 women) and measured (a) standard clinical biomarker concentrations for iron metabolism and (b) an in vivo proxy for glutamate concentration, glutamate with glutamine in relation to total creatine containing metabolites using proton magnetic resonance spectroscopy studies with a two‐dimensional chemical shift imaging slice, with voxels located in bilateral dorsolateral prefrontal cortices, anterior cingulate cortices and frontal white matter. Only the female group reported significant associations between peripheral markers of iron metabolism and Glx:tCr concentration: (a) right dorsolateral prefrontal cortex Glx:tCr associated positively with serum transferrin (r = .60, p = .006) and negatively with transferrin saturation (r = −.62, p = .004) and (b) right frontal white matter Glx:tCr associated negatively with iron concentration (r = −.59, p = .008) and transferrin saturation (r = −.65, p = .002). Our results support associations between iron metabolism and our proxy for in vivo glutamate concentration (Glx:tCr). These associations were limited to women, suggesting a stronger regulatory control between iron and glutamate metabolism. These associations support additional fundamental research into the molecular mechanisms of this regulatory control. Research reports associations between glutamate and iron metabolism and these differ by sex, limited in vivo human studies have been performed to investigate this. Healthy adults’ in vivo glutamate, Glx:tCr 1H‐MRS and peripheral iron markers were measured. Female right hemisphere dorsolateral prefrontal cortex and frontal white matter voxels reported significant associations between Glx:tCr and iron. These associations suggest stronger regulatory control in women.