scholarly journals Excitatory/inhibitory neuronal metabolic balance in mouse hippocampus upon infusion of [U-13C6]glucose

2020 ◽  
pp. 0271678X2091053
Author(s):  
Antoine Cherix ◽  
Guillaume Donati ◽  
Blanca Lizarbe ◽  
Bernard Lanz ◽  
Carole Poitry-Yamate ◽  
...  
Keyword(s):  
Critical Role ◽  
Tca Cycle ◽  
Brain Regions ◽  
Inhibitory Neurons ◽  
Resonance Spectroscopy ◽  
Spectral Fitting ◽  
Mouse Hippocampus ◽  
And Behavior ◽  
Gabaergic Activity

Hippocampus plays a critical role in linking brain energetics and behavior typically associated to stress exposure. In this study, we aimed to simultaneously assess excitatory and inhibitory neuronal metabolism in mouse hippocampus in vivo by applying 18FDG-PET and indirect 13C magnetic resonance spectroscopy (1H-[13C]-MRS) at 14.1 T upon infusion of uniformly 13C-labeled glucose ([U-13C6]Glc). Improving the spectral fitting by taking into account variable decoupling efficiencies of [U-13C6]Glc and refining the compartmentalized model by including two γ-aminobutyric acid (GABA) pools permit us to evaluate the relative contributions of glutamatergic and GABAergic metabolism to total hippocampal neuroenergetics. We report that GABAergic activity accounts for ∼13% of total neurotransmission (VNT) and ∼27% of total neuronal TCA cycle (VTCA) in mouse hippocampus suggesting a higher VTCA/VNT ratio for inhibitory neurons compared to excitatory neurons. Finally, our results provide new strategies and tools for bringing forward the developments and applications of 13C-MRS in specific brain regions of small animals.

scholarly journals Region-specific elevations of glutamate + glutamine correlate with the sensory symptoms of autism spectrum disorders

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jason L. He ◽  
Georg Oeltzschner ◽  
Mark Mikkelsen ◽  
Alyssa Deronda ◽  
Ashley D. Harris ◽  
...  
Keyword(s):  
Autism Spectrum Disorders ◽  
Strong Support ◽  
Empirical Support ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Resonance Spectroscopy ◽  
Primary Sensorimotor Cortex ◽  
Spectrum Disorders ◽  
Inhibitory Signaling

AbstractIndividuals on the autism spectrum are often reported as being hyper- and/or hyporeactive to sensory input. These sensory symptoms were one of the key observations that led to the development of the altered excitation-inhibition (E-I) model of autism, which posits that an increase ratio of excitatory to inhibitory signaling may explain certain phenotypical expressions of autism spectrum disorders (ASD). While there has been strong support for the altered E-I model of autism, much of the evidence has come from animal models. With regard to in-vivo human studies, evidence for altered E-I balance in ASD come from studies adopting magnetic resonance spectroscopy (MRS). Spectral-edited MRS can be used to provide measures of the levels of GABA + (GABA + macromolecules) and Glx (glutamate + glutamine) in specific brain regions as proxy markers of inhibition and excitation respectively. In the current study, we found region-specific elevations of Glx in the primary sensorimotor cortex (SM1) in ASD. There were no group differences of GABA+ in either the SM1 or thalamus. Higher levels of Glx were associated with more parent reported difficulties of sensory hyper- and hyporeactivity, as well as reduced feed-forward inhibition during tactile perception in children with ASD. Critically, the finding of elevated Glx provides strong empirical support for increased excitation in ASD. Our results also provide a clear link between Glx and the sensory symptoms of ASD at both behavioral and perceptual levels.

scholarly journals Assessment of Metabolic Fluxes in the Mouse Brain in Vivo Using 1H-[13C] NMR Spectroscopy at 14.1 Tesla

2015 ◽  
Vol 35 (5) ◽  
pp. 759-765 ◽  
Author(s):  
Lijing Xin ◽  
Bernard Lanz ◽  
gxia Lei ◽  
Rolf Gruetter
Keyword(s):  
Mouse Models ◽  
Mouse Brain ◽  
Conversion Rate ◽  
Tca Cycle ◽  
Compartment Model ◽  
13C Nmr Spectroscopy ◽  
Resonance Spectroscopy ◽  
Metabolic Fluxes ◽  
Short Echo Time

13C magnetic resonance spectroscopy (MRS) combined with the administration of 13C labeled substrates uniquely allows to measure metabolic fluxes in vivo in the brain of humans and rats. The extension to mouse models may provide exclusive prospect for the investigation of models of human diseases. In the present study, the short-echo-time (TE) full-sensitivity 1H-[13C] MRS sequence combined with high magnetic field (14.1 T) and infusion of [U-13C6] glucose was used to enhance the experimental sensitivity in vivo in the mouse brain and the 13C turnover curves of glutamate C4, glutamine C4, glutamate+glutamine C3, aspartate C2, lactate C3, alanine C3, γ-aminobutyric acid C2, C3 and C4 were obtained. A one-compartment model was used to fit 13C turnover curves and resulted in values of metabolic fluxes including the tricarboxylic acid (TCA) cycle flux VTCA (1.05 ± 0.04 μmol/g per minute), the exchange flux between 2-oxoglutarate and glutamate Vx (0.48 ± 0.02 μmol/g per minute), the glutamate-glutamine exchange rate Vgln (0.20 ± 0.02 μmol/g per minute), the pyruvate dilution factor Kdil (0.82 ± 0.01), and the ratio for the lactate conversion rate and the alanine conversion rate VLac/ VAla (10 ± 2). This study opens the prospect of studying transgenic mouse models of brain pathologies.

scholarly journals Focal changes in brain energy and phospholipid metabolism in first-episode schizophrenia

2004 ◽  
Vol 184 (5) ◽  
pp. 409-415 ◽  
Author(s):  
J. Eric Jensen ◽  
Jodi Miller ◽  
Peter C. Williamson ◽  
Richard W J. Neufeld ◽  
Ravi S. Menon ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Imaging Techniques ◽  
High Energy ◽  
Brain Regions ◽  
Anterior Cingulate ◽  
First Episode ◽  
Resonance Spectroscopy ◽  
Membrane Breakdown ◽  
First Episode Schizophrenia

BackgroundMembrane phospholipid and high-energy abnormalities measured with phosphorus magnetic resonance spectroscopy (31P-MRS) have been reported in patients with schizophrenia in several brain regions.AimsUsing improved imaging techniques, previously inaccessible brain regions were examined in patients with first-episode schizophrenia and healthy volunteers with 4.0 T 31P-MRS.MethodBrain spectra were collected in vivo from 15 patients with first-episode schizophrenia and 15 healthy volunteers from 15 cm3 effective voxels in the thalamus, cerebellum, hippocampus, anterior/posterior cingulate, prefrontal cortex and parieto-occipital cortex.ResultsPeople with first-episode schizophrenia showed increased levels of glycerophosphocholine in the anterior cingulate. Inorganic phosphate, phosphocreatine and adenosine triphosphate concentrations were also increased in the anterior cingulate in this group.ConclusionsThe increased phosphodiester and high-energy phosphate levels in the anterior cingulate of brains of people with first-episode schizophrenia may indicate neural overactivity in this region during the early stages of the illness, resulting in increased excitotoxic neural membrane breakdown.

scholarly journals Compartmentalised energy metabolism supporting glutamatergic neurotransmission in response to increased activity in the rat cerebral cortex: A 13C MRS study in vivo at 14.1 T

2016 ◽  
Vol 36 (5) ◽  
pp. 928-940 ◽  
Author(s):  
Sarah Sonnay ◽  
João MN Duarte ◽  
Nathalie Just ◽  
Rolf Gruetter
Keyword(s):  
Energy Metabolism ◽  
Tca Cycle ◽  
Resonance Spectroscopy ◽  
Activity Levels ◽  
Rat Cortex ◽  
Metabolic Compartmentation ◽  
Specific Regulation ◽  
A Minor ◽  
Stimulation Of

Many tissues exhibit metabolic compartmentation. In the brain, while there is no doubt on the importance of functional compartmentation between neurons and glial cells, there is still debate on the specific regulation of pathways of energy metabolism at different activity levels. Using 13C magnetic resonance spectroscopy (MRS) in vivo, we determined fluxes of energy metabolism in the rat cortex under α-chloralose anaesthesia at rest and during electrical stimulation of the paws. Compared to resting metabolism, the stimulated rat cortex exhibited increased glutamate–glutamine cycle (+67 nmol/g/min, +95%, P < 0.001) and tricarboxylic (TCA) cycle rate in both neurons (+62 nmol/g/min, +12%, P < 0.001) and astrocytes (+68 nmol/g/min, +22%, P = 0.072). A minor, non-significant modification of the flux through pyruvate carboxylase was observed during stimulation (+5 nmol/g/min, +8%). Altogether, this increase in metabolism amounted to a 15% (67 nmol/g/min, P < 0.001) increase in CMRglc(ox), i.e. the oxidative fraction of the cerebral metabolic rate of glucose. In conclusion, stimulation of the glutamate–glutamine cycle under α-chloralose anaesthesia is associated to similar enhancement of neuronal and glial oxidative metabolism.

scholarly journals The effects of therapeutic hypothermia on cerebral metabolism in neonates with hypoxic-ischemic encephalopathy: An in vivo 1H-MR spectroscopy study

2015 ◽  
Vol 36 (6) ◽  
pp. 1075-1086 ◽  
Author(s):  
Jessica L Wisnowski ◽  
Tai-Wei Wu ◽  
Aaron J Reitman ◽  
Claire McLean ◽  
Philippe Friedlich ◽  
...  
Keyword(s):  
Therapeutic Hypothermia ◽  
Energy Demand ◽  
Cerebral Metabolism ◽  
Brain Regions ◽  
Hypoxic Ischemic Encephalopathy ◽  
Cerebral White Matter ◽  
Similar Degree ◽  
Resonance Spectroscopy ◽  
Ischemic Encephalopathy

Therapeutic hypothermia has emerged as the first empirically supported therapy for neuroprotection in neonates with hypoxic-ischemic encephalopathy (HIE). We used magnetic resonance spectroscopy (1H-MRS) to characterize the effects of hypothermia on energy metabolites, neurotransmitters, and antioxidants. Thirty-one neonates with HIE were studied during hypothermia and after rewarming. Metabolite concentrations (mmol/kg) were determined from the thalamus, basal ganglia, cortical grey matter, and cerebral white matter. In the thalamus, phosphocreatine concentrations were increased by 20% during hypothermia when compared to after rewarming (3.49 ± 0.88 vs. 2.90 ± 0.65, p < 0.001) while free creatine concentrations were reduced to a similar degree (3.00 ± 0.50 vs. 3.74 ± 0.85, p < 0.001). Glutamate (5.33 ± 0.82 vs. 6.32 ± 1.12, p < 0.001), aspartate (3.39 ± 0.66 vs. 3.87 ± 1.19, p < 0.05), and GABA (0.92 ± 0.36 vs. 1.19 ± 0.41, p < 0.05) were also reduced, while taurine (1.39 ± 0.52 vs. 0.79 ± 0.61, p < 0.001) and glutathione (2.23 ± 0.41 vs. 2.09 ± 0.33, p < 0.05) were increased. Similar patterns were observed in other brain regions. These findings support that hypothermia improves energy homeostasis by decreasing the availability of excitatory neurotransmitters, and thereby, cellular energy demand.

scholarly journals Whole-Brain High-Resolution Metabolite Mapping with 3D Compressed-Sensing-SENSE-LowRank 1H FID-MRSI

2020 ◽  
Author(s):  
Antoine Klauser ◽  
Paul Klauser ◽  
Frédéric Grouiller ◽  
Sebastien Courvoisier ◽  
Francois Lazeyras
Keyword(s):  
High Resolution ◽  
Brain Regions ◽  
Low Rank ◽  
Acquisition Time ◽  
Resonance Spectroscopy ◽  
Brain Anatomy ◽  
Reconstruction Technique ◽  
Whole Brain ◽  
Isotropic Resolution

There is a growing interest of the neuroscience community to map the distribution of brain metabolites in vivo. Magnetic resonance spectroscopy imaging (MRSI) is often limited by either a poor spatial resolution and/or a long acquisition time which severely limits its applications for clinical or research purposes. We developed a novel acquisition-reconstruction technique combining fast 1H-FID-MRSI sequence accelerated by random k-space undersampling and a low-rank and total-generalized variation (TGV) constrained model. This framework was applied to the brain of four healthy volunteers. Following 20 min acquisition, reconstruction and quantification, the resulting metabolic maps with a 5 mm isotropic resolution reflected the detailed neurochemical composition of all brain regions and revealed part of the underlying brain anatomy. Contrasts and features from the 3D metabolite distributions were in agreement with the literature and consistent across the four subjects. The successful combination of the 3D 1H-FID-MRSI with a constrained reconstruction enables the detailed mapping of metabolite concentrations at high-resolution in the whole brain and with an acquisition time that is compatible with clinical or research settings.

scholarly journals Hypothyroidism Decreases the Biogenesis in Free Mitochondria and Neuronal Oxygen Consumption in the Cerebral Cortex of Developing Rats

Endocrinology ◽  
2009 ◽  
Vol 150 (8) ◽  
pp. 3953-3959 ◽  
Author(s):  
Bienvenida Martinez ◽  
Tiago B. Rodrigues ◽  
Elena Gine ◽  
John P. Kaninda ◽  
Ana Perez-Castillo ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Oxygen Consumption ◽  
Thyroid Hormone ◽  
Critical Role ◽  
Neural Population ◽  
Resonance Spectroscopy ◽  
13C Nuclear Magnetic Resonance ◽  
Respiratory Complex I ◽  
Flow Through

Thyroid hormone plays a critical role in mitochondrial biogenesis in two areas of the developing brain, the cerebral cortex and the striatum. Here we analyzed, in the cerebral cortex of neonatal rats, the effect of hypothyroidism on the biogenesis in free and synaptosomal mitochondria by analyzing, in isolated mitochondria, the activity of respiratory complex I, oxidative phosphorylation, oxygen consumption, and the expression of mitochondrial genome. In addition, we studied the effect of thyroid hormone in oxygen consumption in vivo by determining metabolic flow through 13C nuclear magnetic resonance spectroscopy. Our results clearly show that in vivo, hypothyroidism markedly reduces oxygen consumption in the neural population of the cerebral cortex. This effect correlates with decreased free mitochondria biogenesis. In contrast, no effect was observed in the biogenesis in synaptosomal mitochondria. The parameters analyzed were markedly improved after T3 administration. These results suggest that a reduced biogenesis and the subsequent reduction of respiratory capacity in free mitochondria could be the underlying cause of decreased oxygen consumption in the neurons of the cerebral cortex of hypothyroid neonates.

scholarly journals Acute Ethanol-Induced Changes in Edema and Metabolite Concentrations in Rat Brain

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Huimin Liu ◽  
Wenbin Zheng ◽  
Gen Yan ◽  
Baoguo Liu ◽  
Lingmei Kong ◽  
...  
Keyword(s):  
Rat Brain ◽  
Frontal Lobes ◽  
Brain Regions ◽  
Ethanol Administration ◽  
Resonance Spectroscopy ◽  
Cytotoxic Edema ◽  
Acute Ethanol ◽  
Adc Values ◽  
Cerebral Metabolites

The aim of this study is to describe the acute effects of EtOH on brain edema and cerebral metabolites, using diffusion weight imaging (DWI) and proton magnetic resonance spectroscopy (1H-MRS) at a 7.0T MR and to define changes in apparent diffusion coefficient (ADC) values and the concentration of metabolites in the rat brain after acute EtOH intoxication. ADC values in each ROI decreased significantly at 1 h and 3 h after ethanol administration. ADC values in frontal lobe were decreased significantly compared with other regions at 3 h. For EtOH/Cr+PCr and cerebral metabolites (Cho, Tau, and Glu) differing over time, no significant differences for Ins, NAA, and Cr were observed in frontal lobes. Regression analysis revealed a significant association between TSEtOH/Cr+PCrand TSCho, TSTau, TSGlu, and TSADC. The changes of ADC values in different brain regions reflect the process of the cytotoxic edema in vivo. The characterization of frontal lobes metabolites changes and the correlations between TSEtOH/Cr+PCrand TSCho, TSTau, and TSGluprovide a better understanding for the biological mechanisms in neurotoxic effects of EtOH on the brain. In addition, the correlations between TSEtOH/Cr+PCrand TSADCwill help us to understand development of the ethanol-induced brain cytotoxic edema.

Magnetic Resonance Spectroscopy and its Applications in Psychiatry

2002 ◽  
Vol 36 (1) ◽  
pp. 31-43 ◽  
Author(s):  
Gin S. Malhi ◽  
Michael Valenzuela ◽  
Wei Wen ◽  
Perminder Sachdev
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Brain Regions ◽  
Response To Treatment ◽  
Resonance Spectroscopy ◽  
Biochemical Basis ◽  
Non Invasive ◽  
Investigative Technique ◽  
Neurochemical Changes

Objective: This paper briefly describes neuroimaging using magnetic resonance spectroscopy (MRS) and provides a systematic review of its application to psychiatric disorders. Method: A literature review ( Index Medicus/ Medline) was carried out, as well as a review of other relevant papers and data known to the authors. Results: Magnetic resonance spectroscopy is a complex and sophisticated neuroimaging technique that allows reliable and reproducible quantification of brain neurochemistry provided its limitations are respected. In some branches of medicine it is already used clinically, for instance, to diagnose tumours and in psychiatry its applications are gradually extending beyond research. Neurochemical changes have been found in a variety of brain regions in dementia, schizophrenia and affective disorders and promising discoveries have also been made in anxiety disorders. Conclusions: Magnetic resonance spectroscopy is a non-invasive investigative technique that has provided useful insights into the biochemical basis of many neuropsychiatric disorders. It allows direct measurement, in vivo, of medication levels within the brain and has made it possible to track the neurochemical changes that occur as a consequence of disease and ageing or in response to treatment. It is an extremely useful advance in neuroimaging technology and one that will undoubtedly have many clinical uses in the near future.

scholarly journals GABA—from Inhibition to Cognition: Emerging Concepts

2017 ◽  
Vol 24 (5) ◽  
pp. 501-515 ◽  
Author(s):  
T. Schmidt-Wilcke ◽  
E. Fuchs ◽  
K. Funke ◽  
A. Vlachos ◽  
F. Müller-Dahlhaus ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Brain Regions ◽  
Mammalian Brain ◽  
Resonance Spectroscopy ◽  
Inhibitory Neurotransmitter ◽  
Electrophysiological Properties ◽  
Potential Strategy ◽  
The One ◽  
And Behavior

Neural functioning and plasticity can be studied on different levels of organization and complexity ranging from the molecular and synaptic level to neural circuitry of whole brain networks. Across neuroscience different methods are being applied to better understand the role of various neurotransmitter systems in the evolution of perception and cognition. GABA is the main inhibitory neurotransmitter in the adult mammalian brain and, depending on the brain region, up to 25% of the total number of cortical neurons are GABAergic interneurons. At the one end of the spectrum, GABAergic neurons have been accurately described with regard to cell morphological, molecular, and electrophysiological properties; at the other end researchers try to link GABA concentrations in specific brain regions to human behavior using magnetic resonance spectroscopy. One of the main challenges of modern neuroscience currently is to integrate knowledge from highly specialized subfields at distinct biological scales into a coherent picture that bridges the gap between molecules and behavior. In the current review, recent findings from different fields of GABA research are summarized delineating a potential strategy to develop a more holistic picture of the function and role of GABA.

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