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

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.