Net increase of lactate and glutamate concentration in activated human visual cortex detected with magnetic resonance spectroscopy at 7 tesla

After the landmark studies reporting changes in the cerebral metabolic rate of glucose (CMR(Glc) ) in excess of those in oxygen (CMR(O2) ) during physiological stimulation, several studies have examined the fate of the extra carbon taken up by the brain, reporting a wide range of changes in brain lactate from 20% to 250%. The present study reports functional magnetic resonance spectroscopy measurements at 7 Tesla using the enhanced sensitivity to study a small cohort (n = 6). Small increases in lactate (19% ± 4%, P < 0.05) and glutamate (4% ± 1%, P < 0.001) were seen within the first 2 min of activation. With the exception of glucose (12% ± 5%, P < 0.001), no other metabolite concentration changes beyond experimental error were significantly observed. Therefore, the present study confirms that lactate and glutamate changes during physiological stimulation are small (i.e. below 20%) and shows that the increased sensitivity allows reproduction of previous results with fewer subjects. In addition, the initial rate of glutamate and lactate concentration increases implies an increase in CMR(O2) that is slightly below that of CMR(Glc) during the first 1-2 min of activation. © 2013 Wiley Periodicals, Inc.

Astrocytic and neuronal oxidative metabolism are coupled to the rate of glutamate-glutamine cycle in the tree shrew visual cortex

Anne Catherine Clerc, João Miguel das Neves Duarte, Rolf Gruetter, Nathalie Just, Gregor Rainer, Sarah Catherine Sonnay

Astrocytes play an important role in glutamatergic neurotransmission, namely by clearing synaptic glutamate and converting it into glutamine that is transferred back to neurons. The rate of this glutamate–glutamine cycle (VNT) has been proposed to couple to that of glucose utilization and of neuronal tricarboxylic acid (TCA) cycle. In this study, we tested the hypothesis that glutamatergic neurotransmission is also coupled to the TCA cycle rate in astrocytes. For that we investigated energy metabolism by means of magnetic resonance spectroscopy (MRS) in the primary visual cortex of tree shrews (Tupaia belangeri) under light isoflurane anesthesia at rest and during continuous visual stimulation. After identifying the activated cortical volume by blood oxygenation level-dependent functional magnetic resonance imaging, 1H MRS was performed to measure stimulation-induced variations in metabolite concentrations. Relative to baseline, stimulation of cortical activity for 20 min caused a reduction of glucose concentration by −0.34 ± 0.09 µmol/g (p < 0.001), as well as a −9% ± 1% decrease of the ratio of phosphocreatine-to-creatine (p < 0.05). Then 13C MRS during [1,6-13C]glucose infusion was employed to measure fluxes of energy metabolism. Stimulation of glutamatergic activity, as indicated by a 20% increase of VNT, resulted in increased TCA cycle rates in neurons by 12% ( math formula, p < 0.001) and in astrocytes by 24% ( math formula, p = 0.007). We further observed linear relationships between VNT and both math formula and math formula. Altogether, these results suggest that in the tree shrew primary visual cortex glutamatergic neurotransmission is linked to overall glucose oxidation and to mitochondrial metabolism in both neurons and astrocytes.

Wiley-Blackwell2018

Characterization of sustained BOLD activation in the rat barrel cortex and Neurochemical consequences

Hanne Frenkel, Rolf Gruetter, Nathalie Just, Lijing Xin

To date, only a couple of functional MR spectroscopy (fMRS) studies were conducted in rats. Due to the low temporal resolution of 1H-MRS techniques, prolonged stimulation paradigms are necessary for investigating the metabolic outcome in the rat brain during functional challenge. However, sustained activation of cortical areas is usually difficult to obtain due to neural adaptation. Anesthesia, habituation, high variability of the basal state metabolites concentrations as well as low concentrations of the metabolites of interest such as (lactate (Lac), glucose (Glc) or gamma-amminobutyric acid (GABA)) and small expected changes of metabolite concentrations need to be addressed. In the present study, the rat barrel cortex was reliably and reproducibly activated through sustained trigeminal nerve (TGN) stimulation. In addition, TGN stimulation induced significant positive changes in lactate (+1.01mumol/g, p

Elsevier2013

In vivo magnetic resonance spectroscopy of human brain: the biophysical basis of dementia

Rolf Gruetter

Nuclear magnetic resonance spectroscopy (MRS) in low and medium magnetic fields yields well-resolved natural abundance proton and decoupled phosphorus spectra from small (1-10 cc) volumes of brain in vivo in minutes. With this tool, neurochemical research has advanced through identification and non-invasive assay of specific neuronal--(N-acetylaspartate), glial (myo-inositol)--markers, energetics and osmolytes, and neurotransmitters (glutamate, GABA). From these simple measurements, several dozen disease states are recognized, including birth injury, and white matter and Alzheimer disease. Addition of stable isotopes of carbon (in man) or nitrogen (in experimental animals) has provided in vivo assays of enzyme flux through glucose transport, glycolysis, TCA-cycle, and the glutamine-glutamate-GABA system. Finally, a number of xenobiotics are recognized with heteronuclear NMR techniques. Together, these tools are having a major impact on neuroscience and clinical medicine. Through diagnosis and therapeutic monitoring, a new generation of in vivo metabolite imaging is expected with the advent of conforming RF coils and higher field NMR systems.

Elsevier1998

Astrocytic and neuronal oxidative metabolism are coupled to the rate of glutamate-glutamine cycle in the tree shrew visual cortex

Anne Catherine Clerc, João Miguel das Neves Duarte, Rolf Gruetter, Nathalie Just, Gregor Rainer, Sarah Catherine Sonnay

Wiley-Blackwell2018