Metabonomics studies of urine from mice with early-stage Alzheimer's disease / 浙江大学学报·医学版

OBJECTIVE@#To investigate the metabolic profiles of urine from mice with early-stage Alzheimer's disease (AD).@*METHODS@#Urine samples were collected from 13 mice of 16 weeks and 15 wild-type mice. H-NMR spectroscopy was acquired with a one-dimensional NOESY pulse sequence, and the integral values were imported to SIMCA-P+12.0 software for analysis.@*RESULTS@#The metabonomic analysis showed that the metabolic profiles of the mice were significantly different from that of age-matched wild-type mice. The levels of 3-hydroxybutyrate, 2-hydroxybutyrate, succinic acid, 2-ketoglutaric acid, citric acid, cis-aconitic acid, fumaric acid decreased, and those of acetic acid, trimethylamine, taurine, creatinine, hippuric acid, formic acid, trigonelline, urea increased (all <0.05).@*CONCLUSIONS@#Metabolic pathways including glucose metabolism and methylamine metabolism may be involved in the pathogenesis of early AD.

Sodium pyruvate protect occipital cortex of rats with repetitive and severe neonatal hypoglycemia detected by high resolution 1H nuclear magnetic resonance spectroscopy / 中华围产医学杂志

Objectives To investigate the occipital cortex metabolite alterations in repetitive and severe neonatal hypoglycemia rats treated with sodium pyruvate and to reveal the protective role of sodium pyruvate using high resolution 1H nuclear magnetic resonance spectroscopy.Methods Thirty-six 2-dayold Sprague-Dawley rats were randomly divided into hypoglycemia group and pyruvate group with 18 rats in each group.Rats in both groups received intraperitoneal injections of insulin (40 U/kg body weight) at 2,4 and 6 days of age to induce severe hypoglycemia (blood glucose value ≤ 1.4 mmol/L).In the hypoglycemia group,2.5 hours after insulin injection,intraperitoneal injection of 50％ glucose (2 ml/kg) was administered to terminate hypoglycemia,while in the pyruvate group,50％ glucose (2 ml/kg) and sodium pyruvate solution 2.5 ml/kg (500 mg/kg) were injected.Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay was used to observe the status of injured neurons in six neonatal rats,and metabolite changes in occipital cortex of the other 12 rats were detected by 1H nuclear magnetic resonance spectroscopy.The difference between the two groups was compared by independent-samples t test.Results Neonatal rats of both groups reached severe hypoglycemia level 2.5 hours after insulin injection.Compared with hypoglycemia group,pyruvate group had fewer injured neurons (45±5 vs 113 ± 12,t=0.782,P=0.013) and lower injured index in the occipital cortex (0.15 ± 0.03 vs 0.36 ± 0.06,t=l.143,P=0.020).Pyruvate group showed significant decreases in the concentration of taurine [(13.31 ± 2.06) vs (18.44 ± 3.86) mol/kg,t=8.231],glutamine[(1.50 ± 0.24) vs (2.02 ± 0.40) mol/kg,t=3.137],glutamate[(7.04 ± 0.95) vs (9.40 ± 1.73) mol/kg,t=6.449],aspartate[(1.51 ± 0.28) vs (2.15 ± 0.58) mol/kg,t=2.561] and creatine [(6.37±0.99) vs (8.46± 1.77) mol/kg,t =4.226] in the occipital cortex (all P'＜0.017).Conclusions Simultaneous use of glucose and sodium pyruvate to terminate hypoglycemia in repetitive and severe neonatal hypoglycemia rats can effectively alleviate severe hypoglycemia-induced occipital lobe damage via regulating excitatory amino acid neurotransmitters,energy metabolism and other metabolic pathways.

Studies on Changes of Brain Energy Metabolism in Diabetic Rats by 31 P Magnetic Resonance Spectroscopy / 分析化学

Considerable attention has been directed toward studying the impact of diabetes on the central nervous system. The current study investigates the biochemical changes in the brain tissue of streptozotocin (STZ)-induced diabetic rat using 31P magnetic resonance spectroscopy (31P MRS). The 31P NMR spectra of the whole brain show no significant changes of phosphomonoesters and phosphodiesters levels one week after STZ induction, suggesting no apparent structural changes in cell membranes. The results identifies the increased level of adenosine diphosphate, negligible changes of phosphocreatine ( PCr ) and adenosine triphosphate ( ATP) , but the decreased ratio of PCr/ATP, indicating that PCr plays a role of balancing the energy. Moreover, the decreased pH value indicates the changes of the intracellular environment in STZ-diabetic brains in rats. After 15 weeks of STZ injection, the metabolism of phospholipid membrane and brain energy metabolism has been obviously disturbed. Our study successfully shows that 31 P MRS can not only study phospholipid and energy metabolism non-invasively, but also measure intracellular pH and other important biochemical information. All of these spectroscopic characterizations contribute significantly to the understanding of pathogenesis and evolution of diabetes, and provide theoretical basis for early diagnosis and clinical treatment in diabetes.