Proton magnetic resonance spectroscopy of brain metabolic shifts induced by acute administration of 2‐deoxy‐d‐glucose and lipopolysaccharides

Abstract

In vivo proton magnetic resonance spectroscopy ((1) H MRS) of outbred stock ICR male mice (originating from the Institute of Cancer Research) was used to study the brain (hippocampus) metabolic response to the pro-inflammatory stimulus and to the acute deficiency of the available energy, which was confirmed by measuring the maximum oxygen consumption. Inhibition of glycolysis by means of an injection with 2-deoxy-d-glucose (2DG) reduced the levels of gamma-aminobutyric acid (GABA, p < 0.05, in comparison with control, least significant difference (LSD) test), N-acetylaspartate (NAA, p < 0.05, LSD test) and choline compounds, and at the same time increased the levels of glutamate and glutamine. An opposite effect was found after injection with bacterial lipopolysaccharide (LPS) - a very common pro-inflammatory inducer. An increase in the amounts of GABA, NAA and choline compounds in the brain occurred in mice treated with LPS. Different metabolic responses to the energy deficiency and the pro-inflammatory stimuli can explain the contradictory results of the brain (1) H MRS studies under neurodegenerative pathology, which is accompanied by both mitochondrial dysfunction and inflammation. The prevalence of the excitatory metabolites such as glutamate and glutamine in 2DG treated mice is in good agreement with excitation observed during temporary reduction of the available energy under acute hypoxia or starvation. In turn, LPS, as an inducer of the sickness behavior, which was manifested as depression, sleepiness, loss of appetite etc., shifts the brain metabolic pattern toward the prevalence of the inhibitory neurotransmitter GABA.

Effects of a compound from the group of substituted thiadiazines with hypothermia inducing properties on brain metabolism in rats, a study in vivo and in vitro

“…Altered brain energy turnover inevitably affects balance of most abundant brain metabolites [24]. Several brain metabolites were measured in vivo in rat cortex using magnetic resonance spectroscopy.…”

“…The experimental 1 H magnetic resonance spectra were processed and the quantitative composition of metabolites was determined with an original specialized program developed in our laboratory [24] similar to the LCModel software package [25], assuming that the spectrum of a mixture of known compounds is a linear combination of analyzed components.…”

Stress‐sensitive arterial hypertension, haemodynamic changes and brain metabolites in hypertensive ISIAH rats: MRI investigation

“…The details of the data processing were published recently (Moshkin et al . ). The background accounting is conducted automatically by the program, in order to determine the spectral baseline for fitting of the spectrum obtained by 1 H MRS.…”

The effect of a single administration of streptozotocin on hippocampus metabolites in NODSCID mice

“…Спектры были обработаны специализированной про-граммой, разработанной сотрудниками ИЦиГ СО РАН (Moshkin et al, 2014), по принципам аналогичной про-граммному обеспечению LCModel (Provencher, 1993). Полученные спектры содержали пики следующих сое ди -нений: мио-инозитол, глицин, креатин, глутамат/ глута-мин, таурин, холиновые компоненты, аспартат, N-аце тил-аспартат, гамма-аминомасляная кислота (ГАМК), лак тат, аланин, фосфорилэтаноламин.…”

“…Большинство исследований in vivo нарушений мозгового метаболизма на животных моделях сосредоточено на МРС гиппокампа (Biessels et al, 2001;Duarte et al, 2009;Wang et al, 2012;Moshkin et al, 2014), что обусловлено особенностями его организации и повышенной реакцией на воздействия (Revsin et al, 2009). И несмотря на то, что МРС головного мозга обладает относительно слабой селективностью, определяемые в ходе исследования ме-таболиты регистрируются как в нейронах и клетках глии, так и в межклеточном пространстве, результаты исследо-ваний актуальны для решения многих практических задач.…”