In vivo neurochemical profiling of rat brain by ¹H‐[¹³C] NMR spectroscopy: cerebral energetics and glutamatergic/GABAergic neurotransmission

Abstract

The quantification of excitatory and inhibitory neurotransmission and the associated energy metabolism is crucial for a proper understanding of brain function. Although the detection of glutamatergic neurotransmission in vivo by 13 C NMR spectroscopy is now relatively routine, the detection of GABAergic neurotransmission in vivo has remained elusive because of the low GABA concentration and spectral overlap. Using 1 H-[ 13 C] NMR spectroscopy at high magnetic field in combination with robust spectral modeling and the use of different substrates, [U-13 C 6 ]-glucose and [2-13 C]-acetate, it is shown that GABAergic, as well as glutamatergic neurotransmitter fluxes can be detected non-invasively in rat brain in vivo.

Metabolic Flux and Compartmentation Analysis in the Brain In vivo

“…In particular, V TCA in astrocytes and/or V PC were systematically constrained as $V_{\text{PC}}=0.2V_{\text{GS}}$ and $V_{\text{TCA}}^{\text{total}}$ (61, 114). Other studies determined V TCA in the astrocytic compartment from experiments upon [2- 13 C]acetate infusion and the obtained flux is used as constraint to the metabolic modeling of 13 C-labeled glucose experiments for simultaneous determination of fluxes in glutamatergic and/or GABAergic neurons (115). In contrast, in studies that considered all metabolic fluxes as independent parameters, there was a fairly linear relation between pyruvate carboxylation rate ( V PC ) and the glutamate/GABA-glutamine cycle (Figure 8).…”

Quantitative fMRI and oxidative neuroenergetics

“…Hence in the awake brain approximately 80% of the neuronal energy demand is devoted to events associated with neuronal signaling, which contrasted expectations at the time that majority of resting brain energy not being related to signaling (see discussion above). 13 C MRS experiments looking simultaneously at neuronal energy consumption and the rate of the glutamate glutamine cycle have subsequently been performed by several laboratories in both rats and humans (Bluml et al, 2002; Boumezbeur et al, 2010; Chen et al, 2001; Chhina et al, 2001; Choi et al, 2002; Chowdhury et al, 2007; de Graaf et al, 2004; Duarte et al, 2011; Gruetter et al, 2001; Gruetter et al, 1998; Henry et al, 2010; Jiang et al, 2011; Lebon et al, 2002; Mason et al, 1995; Mason et al, 2007; Oz et al, 2004; Pan et al, 2000; Patel et al, 2005a; Patel et al, 2005b; Serres et al, 2008; Shen et al, 1999; van Eijsden et al, 2010; Wang et al, 2010; Yang and Shen, 2005). The results of these studies have been highly consistent with the original findings of Sibson et al and furthermore the human results also agree with the findings in rodent brain (Figure 1).…”

Cortical Substrate Oxidation during Hyperketonemia in the Fasted Anesthetized Rat in Vivo

“…The measured neuronal TCA cycle rate in 36 hourfasted rats is similar to that seen in overnight-fasted, halothane-anesthetized rats infused with [1,6-13 C] or [U-13 C]glucose (0.47 to 0.55 mmol/g per min, van Eijsden et al, 2010;Jiang et al, 2009;Patel et al, 2004). In the latter studies, glucose accounts for > 90% of oxidized substrate, such that V pdhN EV tcaN .…”