Characteristic Metabolic Alterations Identified in Primary Neurons Under High Glucose Exposure

Abstract

Cognitive dysfunction is a central nervous system (CNS) complication of diabetes mellitus (DM) that is characterized by impaired memory and cognitive ability. An in-depth understanding of metabolic alterations in the brain associated with DM will facilitate our understanding of the pathogenesis of cognitive dysfunction. The present study used an in vitro culture of primary neurons in a high-glucose (HG) environment to investigate characteristic alterations in neuron metabolism using nuclear magnetic resonance (NMR)-based metabonomics. High performance liquid chromatography (HPLC) was also used to measure changes in the adenosine phosphate levels in the hippocampal regions of streptozotocin (STZ)-induced diabetic rats. Our results revealed significant elevations in phosphocholine and ATP production in neurons and decreased formate, nicotinamide adenine dinucleotide (NAD+), tyrosine, methionine, acetate and phenylalanine levels after HG treatment. However, the significant changes in lactate, glutamate, taurine and myo-inositol levels in astrocytes we defined previously in astrocytes, were not found in neurons, suggested cell-specific metabolic alterations. We also confirmed an astrocyte-neuron lactate shuttle between different compartments in the brain under HG conditions, which was accompanied by abnormal acetate transport. These alterations reveal specific information on the metabolite levels and transport processes related to neurons under diabetic conditions. Our findings contribute to the understanding of the metabolic alterations and underlying pathogenesis of cognitive decline in diabetic patients.

S100A2 promotes glycolysis and proliferation via GLUT1 regulation in colorectal cancer

“…[35][36][37] Nuclear magnetic resonance (NMR) spectroscopy, which is broadly applied in metabonomic profiles of various diseases. [38][39][40] In this study, 1 H-NMR-based metabolomics highlighted altered metabolic patterns with ectopic expression of S100A2. Plots showed that Glc and Lac were major contributors to the discrimination of metabolic patterns.…”

Analysis of Metabolic Alterations Related to Pathogenic Process of Diabetic Encephalopathy Rats

“…Our studies has indicated that excess lactate is produced in a time-dependent fashion in the hippocampus of diabetic rats (Zheng Y. et al, 2016). Furthermore, using in vitro cultures of primary cells, we demonstrated that astrocytes, but not neurons, excrete more lactate under hyperglycemic conditions (Wang et al, 2018; Zhao et al, 2018b). Simultaneously, using [2- 13 C]acetate and [1- 13 C]glucose as tracer substrates, we observed enhancement of the pyruvate recycling pathway in diabetic rats at 1 week, but not at 15 weeks, suggestive of reduced utilization of lactate in the chronic diabetic stage (Wang et al, 2015).…”

Neither Excessive Nitric Oxide Accumulation nor Acute Hyperglycemia Affects the N-Acetylaspartate Network in Wistar Rat Brain Cells

“…Therefore, the impact of hyperglycemia on the NAA network has been studied using neural stem cells (NSC) instead of primary neurons. Here, we used a widely known in vitro model of hyperglycemia with a daily change of media [ 35 ]. The final glucose concentration in the culture media ranged between 25 and 75 mM (Materials and methods).…”