Anant Bahadur Patel¹ and Kamal Saba^1
1NMR Microimaging and Spectroscopy, CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India

Alzheimer's disease (AD) is the most common neurodegenerative disorders. Currently no effective treatment available for AD. Dietary restriction (DR) has been shown to improve longevity in rodents. In the present study, we evaluated the effects of DR on memory and brain energy metabolism in AβPP-PS1 mouse model of AD using ¹H-[¹³C]-NMR spectroscopy in conjunction with infusion of [1,6-¹³C₂]glucose. Our findings suggest that DR intervention had improved the memory and the neuro-metabolic activity in the AD mice.

Pravin K Mishra¹ and Anant Bahadur Patel^1
1NMR Microimaging and Spectroscopy, CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India

Though, ketamine possess rapid antidepressant properties, its use is limited due to addictive and psychotomimetic properties. In the current study, we have evaluated the antidepressant activity of lanicemine in CUMS model of depression by ¹H-[¹³C]-NMR spectroscopy together with infusion of [1,6-¹³C₂]glucose. Exposure of lanicemine restored behavioral phenotype and activity of excitatory and inhibitory neurons in depression.

Gulin Oz¹, Mauro DiNuzzo², Anjali Kumar³, Amir Moheet³, Kristine Kubisiak⁴, Lynn E. Eberly⁴, and Elizabeth R. Seaquist^3
1Radiology, Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States, ²Museo storico della fisica e Centro di studi e ricerche Enrico Fermi, Rome, Italy, ³Medicine, University of Minnesota, Minneapolis, MN, United States, ⁴Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, United States

Supercompensated brain glycogen levels may contribute to the development of hypoglycemia associated autonomic failure (HAAF) following recurrent hypoglycemia (RH) by providing energy for the brain during subsequent periods of hypoglycemia. To assess the role of glycogen supercompensation in the generation of HAAF, we estimated the level of brain glycogen supercompensation following RH using ¹³C MRS and compared it to that following acute hypoglycemia (AH). Glycogen levels were found to increase after both AH and RH, but to a lesser extent after RH. These data suggest that glycogen supercompensation may be an epiphenomenon of HAAF.

Blanca Lizarbe¹, Antonie Cherix¹, Lijing Xin², Hongxia Lei^2,3, and Rolf Gruetter^1,3,4
1Laboratory for Functional and Metabolic Imaging (LIFMET), Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, ²Animal imaging and technology core (AIT), Center for Biomedical Imaging (CIBM), Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, Lausanne, Switzerland, ³Department of Radiology, University of Geneva, Geneva, Switzerland, ⁴Department of Radiology, University of Lausanne, Lausanne, Switzerland

Obesity is a pandemic syndrome that leads to reduced life expectancy, increasing the risk of heart disease, type-2 diabetes and some type of cancers.  Noteworthy, to understand the mechanisms of obesity onset and development, several animal models, such as administration high fat diets, have been developed. We used ¹H-[¹³C] MRS methods in regular and in high fat diet fed mice to investigate the effects of high caloric diets and obesity in the hypothalamus, its effects in glucose metabolism and metabolic fluxes in neurons and glia. We found differences that suggest impaired glucose metabolism in the hypothalamus of obese mice.

Takashi Watanabe¹, Jens Frahm¹, and Thomas Michaelis^1
1Biomedizinische NMR Forschungs GmbH, Max-Planck-Institut für biophysikalische Chemie, Göttingen, Germany

Using proton MRS/MRI of mouse brain at 9.4 T, this work provides the first in vivo evidence of concurrent pH-dependent changes of amide signals and related metabolic responses to hypercapnia and hypothermia. During hypercapnia, amide MRS signals of glutamine and of unspecific compounds increase by ≥50% at 37°C and 22°C. They are strongly correlated with intracellular pH determined from a shift in creatine phosphokinase equilibrium. In MRI, saturation transfer to water protons alters signal intensities in dependence on pH and temperature. Irradiation of aliphatic compounds at -3.5 ppm frequency offset from water predominantly saturates lipids and water associated with myelin.

Clemence Ligneul^1,2, Marco Palombo^1,2, Juliette Le Douce^1,2, Pierrick Jego^1,2, Martine Guillermier^1,2, Gilles Bonvento^1,2, and Julien Valette^1,2
1CEA/DSV/I2BM/MIRCen, Fontenay-aux-Roses, France, ²CNRS Université Paris-Saclay UMR 9199, Fontenay-aux-Roses, France

In this work we use in vivo MRS and diffusion-weighted MRS to detect alterations in cellular metabolism and structure in a triple transgenic APP/PS1/tauP301L mouse model of Alzheimer’s disease. We are able to detect massive remodeling of metabolic content in the hippocampus, as well as subtle but significant variations in diffusion properties of astrocytic metabolites. These results are essentially consistent with the metabolic and structural signature of activated astrocyte, a cell status represented around amyloid plaques.

Aude-Marie Grapperon¹, Adil Maarouf^2,3, Annie Verschueren¹, Amandine Sevy¹, Elisabeth Soulier², Sylviane Confort-Gouny², Patrick Viout², Jean-Philippe Ranjeva², Maxime Guye^2,3, Sharham Attarian¹, and Wafaa Zaaraoui^2
1APHM, Hôpital Timone, Pôle Neurosciences, Marseille, France, ²CRMBM - CNRS - Aix-Marseille Université, Marseille, France, ³APHM, Hôpital Timone, CEMEREM, Marseille, France

Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease that involves the death of upper (in brain) and lower (in spine) motor neurons. As conventional MRI failed to show brain motor neurons impairment in ALS, advanced techniques are needed to improve the diagnosis of the disease and monitor its progression. ²³Na brain MRI was performed to 4 ALS patients and showed accumulation of sodium in the primary motor areas in the 3 patients presenting with clinical brain motor neuron signs. Besides, more patients were clinically affected, more the sodium accumulation was extended. In conclusion, sodium accumulation, which is an indicator of neuronal injury, could be a marker of ALS diagnosis and disease progression.

Elise Vinckenbosch¹, Mor Mishkovsky¹, Arnaud Comment², and Rolf Gruetter^1,3
1Laboratory of functional and metabolic imaging, EPFL, Lausanne, Switzerland, ²Institute of Physics of Biological Systems, EPFL, Lausanne, Switzerland, ³Department of Radiology, University of Lausanne and Geneva, Lausanne, Switzerland

Hyperpolarized [1-¹³C] acetate enables for in vivo detection of 2-oxoglutarate, a tricarboxylic acid (TCA) cycle intermediate, in intact brain at high field. The aim of this study is to examine saturation substrate dose conditions and to compare it with a partially inhibited TCA cycle model. We conclude that 2-oxoglutarate production rate can be calculated as a function of varying substrate concentrations and is affected as well as the cerebral acetate kinetics by TCA cycle activity modulations.

Evita Wiegers¹, Hanne Rooijackers², Cees Tack², Arend Heerschap¹, Bastiaan de Galan², and Marinette van der Graaf^1,3
1Radiology and Nuclear Medicine, Radboud umc, Nijmegen, Netherlands, ²Internal Medicine, Radboud umc, Nijmegen, Netherlands, ³Pediatrics, Radboud umc, Nijmegen, Netherlands

TThe effect of hypoglycemia on cerebral lactate concentration was assessed in patients with type 1 diabetes (T1DM) and impaired awareness of hypoglycemia (IAH), patients with normal awareness of hypoglycemia (NAH) and in healthy subjects. Brain lactate concentrations were determined during stable euglycemic and stable hypoglycemic conditions using a J-editing semi-LASER ¹H-MRS sequence at 3T. We found a 20% decrease in brain lactate concentration in T1DM patients with IAH in response to hypoglycemia, which may reflect increased lactate oxidation. No changes in cerebral lactate concentrations were observed in the other two groups.

Hui Zhang¹ and Hao Lei^1
1National Center of Magnetic Resonance in Wuhan, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, China, People's Republic of

In this study, we measured regional neurochemical variations in rat prelimbic cortex (PrL)/infralimbic cortex (IL), cingulate cortex (Cg) and retrosplenial cortex (RSC)  with in vivo 1H-MRS at 7T. It was found that the regional metabolic variations follow cytoarchitectural/receptor-architectonical organization in these brain regions.