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Dietary phospholipids (PLs) are promising supplements that are commonly found as natural food ingredients and emulsifier additives. The present study aimed to evaluate the effect of major PLs found in food supplements on social behavior in mice. In this study, the effect of short-term high dietary PL content was studied in terms of social odor discrimination and social interactions with male and female intruders in male mice. We used odor discrimination and habituation tests to demonstrate that PL-fed male mice tend to lose preference toward female odor and fail to discriminate against socially significant scents. At the same time, test animals recognize non-social odors. We also found that PL affected the social behavior of the test males, who tend to behave indiscriminately toward male and female intruders during direct contact. Brain metabolomic profiling revealed no major changes in the intermediary metabolism or neurotransmitter biosynthesis. At the same time, intranasal PL application resembled the effects of dietary supplementation. These data suggest that certain PL might suppress pheromone perception in the olfactory system and affect the sense of socially important odor cues. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is the most common type of dementia in the elderly. Incomplete knowledge about the pathogenesis of this disease determines the absence of medications for the treatment of AD today. Animal models can provide the necessary knowledge to understand the mechanisms of biochemical processes occurring in the body in health and disease. Objective: To identify the most promising metabolomic predictors and biomarkers reflecting metabolic disorders in the development of AD signs. Methods: High resolution 1H NMR spectroscopy was used for quantitative metabolomic profiling of the hippocampus of OXYS rats, an animal model of sporadic AD, which demonstrates key characteristics of this disease. Animals were examined during several key periods: 20 days group corresponds to the "preclinical" period preceding the development of AD signs, during their manifestation (3 months), and active progression (18 months). Wistar rats of the same age were used as control. Results: Ranges of variation and mean concentrations were established for 59 brain metabolites. The main metabolic patterns during aging, which are involved in energy metabolism pathways and metabolic shifts of neurotransmitters, have been established. Of particular note is the significant increase of scyllo-inositol and decrease of hypotaurine in the hippocampus of OXYS rats as compared to Wistars for all studied age groups. Conclusions: We suggest that the accumulation of scyllo-inositol and the reduction of hypotaurine in the brain, even at an early age, can be considered as predictors and potential biomarkers of the development of AD signs in OXYS rats and, probably, in humans. [ABSTRACT FROM AUTHOR]

The Animal Metabolite Database (AMDB, https://amdb.online) is a freely accessible database with built-in statistical analysis tools, allowing one to browse and compare quantitative metabolomics data and raw NMR and MS data, as well as sample metadata, with a focus on the metabolite concentrations rather than on the raw data itself. AMDB also functions as a platform for the metabolomics community, providing convenient deposition and exchange of quantitative metabolomic data. To date, the majority of the data in AMDB relate to the metabolite content of the eye lens and blood of vertebrates, primarily wild species from Siberia, Russia and laboratory rodents. However, data on other tissues (muscle, heart, liver, brain, and more) are also present, and the list of species and tissues is constantly growing. Typically, every sample in AMDB contains concentrations of 60–90 of the most abundant metabolites, provided in nanomoles per gram of wet tissue weight (nmol/g). We believe that AMDB will become a widely used tool in the community, as typical metabolite baseline concentrations in tissues of animal models will aid in a wide variety of fundamental and applied scientific fields, including, but not limited to, animal modeling of human diseases, assessment of medical formulations, and evolutionary and environmental studies. [ABSTRACT FROM AUTHOR]

Dietary composition substantially determines human health and affects complex diseases, including obesity, inflammation and cancer. Thus, food supplements have been widely used to accommodate dietary composition to the needs of individuals. Among the promising supplements are dietary phospholipids (PLs) that are commonly found as natural food ingredients and as emulsifier additives. The aim of the present study was to evaluate the effect of major PLs found as food supplements on the morphology of intestinal epithelial cells upon short-term and long-term high-dose feeding in mice. In the present report, the effect of short-term and long-term high dietary PL content was studied in terms of intestinal health and leaky gut syndrome in male mice. We used transmission electron microscopy to evaluate endothelial morphology at the ultrastructural level. We found mitochondrial damage and lipid droplet accumulation in the intracristal space, which rendered mitochondria more sensitive to respiratory uncoupling as shown by a mitochondrial respiration assessment in the intestinal crypts. However, this mitochondrial damage was insufficient to induce intestinal permeability. We propose that high-dose PL treatment impairs mitochondrial morphology and acts through extensive membrane utilization via the mitochondria. The data suggest that PL supplementation should be used with precaution in individuals with mitochondrial disorders. [ABSTRACT FROM AUTHOR]

Autophagy is involved in the maintenance of cellular homeostasis and the removal of damaged proteins and organelles and is necessary to maintain cell metabolism in conditions of energy and nutrient deficiency. A decrease in autophagic activity plays an important role in age-related diseases. However, the metabolic response to autophagy modulation remains poorly understood. Here, we for the first time explored the effects of (1) autophagy activation by 48 h fasting, (2) inhibition by chloroquine (CQ) treatment, and (3) combined effects of fasting and CQ on the quantitative composition of metabolites in the blood serum of senescent-accelerated OXYS and control Wistar rats at the age of 4 months. By means of high-resolution 1H NMR spectroscopy, we identified the quantitative content of 55 serum metabolites, including amino acids, organic acids, antioxidants, osmolytes, glycosides, purine, and pyrimidine derivatives. Groups of 48 h fasting (induction of autophagy), CQ treatment (inhibition of autophagy), and combined effects (CQ + fasting) are clearly separated from control groups by principal component analysis. Fasting for 48 h led to significant changes in the serum metabolomic profile, primarily affecting metabolic pathways related to fatty acid metabolism, and led to metabolism of several amino acids. Under CQ treatment, the most affected metabolites were citrate, betaine, cytidine, proline, tryptophan, glutamate, and mannose. As shown by two-way ANOVA, for many metabolites the effects of autophagy modulation depend on the animal genotype, indicating a dysregulation of metabolome reactivity in OXYS rats. Thus, the metabolic responses to modulation of autophagy in OXYS rats and Wistar rats are different. Altered metabolites in OXYS rats may serve as potential biomarkers of the manifestation of the signs of accelerated aging. Metabolic signatures characteristic to fasting and CQ treatment revealed in this work might provide a better understanding of the connections between metabolism and autophagy. [ABSTRACT FROM AUTHOR]

The studies on photolysis of aqueous kynurenine (KN) solutions that resulted in the formation of triplet kynurenine (super T)KN* is reported. The main aim is to establish that photoinduced formation of (super T)KN* does indeed take place with UV light excitation, and to provide characterization data on (super T)KN* as a function of pH.

The properties of xanthurenic acid (XAN) in ground and photoexcited states have been studied using steady-state and time-resolved optical methods as well as quantum chemistry calculations. In neutral aqueous solution and in alcohols, XAN is present in a single tautomeric form (keto form), whereas in aprotic solvents and probably in basic aqueous solutions, more than one tautomeric form is present. UV irradiation of aqueous and alcoholic solutions of XAN results in a very rapid solvent-assisted tautomerization to the enol form, the later undergoes solvent-assisted transformation back to the keto form. The photolysis of XAN in aprotic solvents gives rise to the formation of numerous intermediate forms of XAN in both triplet and ground states. Under intense laser irradiation, XAN undergoes biphotonic ionization, the precursor for ionization being the excited singlet state. [ABSTRACT FROM AUTHOR]

(1) Recently, metabolic profiling of the tissue in the native state or extracts of its metabolites has become increasingly important in the field of metabolomics. An important factor, in this case, is the presence of blood in a tissue sample, which can potentially lead to a change in the concentration of tissue metabolites and, as a result, distortion of experimental data and their interpretation. (2) In this paper, the metabolomic profiling based on NMR spectroscopy was performed to determine the effect of blood contained in the studied samples of brain tissue on their metabolomic profile. We used 13 male laboratory CD-1® IGS mice for this study. The animals were divided into two groups. The first group of animals (n = 7) was subjected to the perfusion procedure, and the second group of animals (n = 6) was not perfused. The brain tissues of the animals were homogenized, and the metabolite fraction was extracted with a water/methanol/chloroform solution. Samples were studied by high-frequency 1H-NMR spectroscopy with subsequent statistical data analysis. The group comparison was performed with the use of the Student's test. We identified 36 metabolites in the brain tissue with the use of NMR spectroscopy. (3) For the major set of studied metabolites, no significant differences were found in the brain tissue metabolite concentrations in the native state and after the blood removal procedure. (4) Thus, it was shown that the presence of blood does not have a significant effect on the metabolomic profile of the brain in animals without pathologies. [ABSTRACT FROM AUTHOR]

Growing evidence suggests that intestinal mucosa homeostasis impacts immunity, metabolism, the Central Nervous System (CNS), and behavior. Here, we investigated the effect of the monosaccharide fucose on inflammation, metabolism, intestinal microbiota, and social behavior in the Dextran Sulfate Sodium (DSS)-induced chronic colitis mouse model. Our data show that chronic colitis is accompanied by the decrease of the serum tryptophan level and the depletion of the intestinal microbiota, specifically tryptophan-producing E. coli and Bifidobacterium. These changes are associated with defects in the male mouse social behavior such as a lack of preference towards female bedding in an odor preference test. The addition of fucose to the test animals' diet altered the bacterial community, increased the abundance of tryptophan-producing E. coli, normalized blood tryptophan levels, and ameliorated social behavior deficits. At the same time, we observed no ameliorating effect of fucose on colon morphology and colitis. Our results suggest a possible mechanism by which intestinal inflammation affects social behavior in male mice. We propose fucose as a promising prebiotic, since it creates a favorable environment for the beneficial bacteria that promote normalization of serum tryptophan level and amelioration of the behavioral abnormalities in the odor preference test. [ABSTRACT FROM AUTHOR]

Purpose: To determine the age-related and the cataract-specific changes in the crystallin composition in lenses of accelerated-senescence OXYS (cataract model) and Wistar (control) rats., Methods: The water soluble (WS) and insoluble (WIS) fractions of the lens proteins were separated; the identity and relative abundance of each crystallin in WS fraction were determined with the use of two-dimensional electrophoresis (2-DE) and Matrix-Assisted Laser Desorption Ionization-Time Of Flight (MALDI-TOF) mass spectrometry. All statistical calculations were performed using the software package Statistica 6.0 by factor dispersion analysis (ANOVA/MANOVA) and Newman-Keuls post-hoc test for comparison of group mean values., Results: The WIS protein content increased significantly in the aged animal lenses; the WIS/WS ratio increases in approximately 8 times to the age of 62 weeks. The interstrain difference was insignificant in this experiment. 2-DE maps of the young rat lenses (3 weeks) showed single spots for each lens protein while in older lenses (12 and 62 weeks) each crystallin was presented by several spots. The abundance of γA-γF-crystallins in WS fraction significantly decreases with age. A significant increase in the percentage abundance was also found for α-crystallins and βB2-crystallin from 3 to 12 weeks. The major differences between Wistar and OXYS lenses are the faster decay of the content of γA-γF-crystallins in OXYS lenses, and the significant decrease of unmodified αA-crystallin abundance in old OXYS lenses., Conclusions: The presented results demonstrate that the increase of the water-insoluble (WIS) protein fraction is rather age-specific than cataract-specific phenomenon. The major age-related changes in WS protein composition are the fast insolubilization of γ-crystallins, and the increase of αB- and βB2-crystallin abundance. The main interstrain differences, which could be attributed to the cataract-specific processes, are the faster decay of the content of γ-crystallins and the significant decrease of unmodified αA-crystallin abundance in the OXYS lenses.

Purpose: To determine the levels of kynurenine (KN) and its metabolic precursor tryptophan (Trp) in lenses of accelerated-senescence OXYS (cataract model) and Wistar (control) rats at ages from 1 day to 24 months., Methods: Protein-free lens extracts were prepared from Wistar and senescent-accelerated OXYS rat lenses. The presence and levels of KN and Trp were determined using high performance liquid chromatography (HPLC) analysis and mass spectrometric measurements. All statistical calculations were made using the software package Statistica 6.0, using factor dispersion analysis and Newman-Keuls post-hoc test for comparison of group mean values., Results: The levels of KN, which plays the role of a molecular Ultraviolet (UV) filter in the human lens, and its metabolic precursor Trp in the rat lens significantly depend on the rat strain and age. During the first 20 days after birth, before the first signs of cataract in OXYS rats, there is a strong difference in the content of both Trp and KN between Wistar and OXYS lenses. This difference becomes insignificant in lenses of 1 month and older. The levels of Trp and KN in young lenses are higher than that in lenses of 1 month and older for both strains., Conclusions: The presented results demonstrate that the KN pathway of Trp catabolism does not play a significant role in cataract development in the rat lens at the stages of cataract manifestation; however, in the first 3 weeks of postnatal development, the interstrain difference in KN and Trp levels is very strong. The obtained results show a correlation between the low level of KN and the high level of Trp at the stage of lens maturation and future cataractogenesis, and suggest an imbalance in the KN pathway of Trp catabolism in potentially cataractous lenses.