RatDEGdb: a knowledge base of differentially expressed genes in the rat as a model object in biomedical research.

The animal models used in biomedical research cover virtually every human disease. RatDEGdb, a knowledge base of the differentially expressed genes (DEGs) of the rat as a model object in biomedical research is a collection of published data on gene expression in rat strains simulating arterial hypertension, age-related diseases, psychopathological conditions and other human afflictions. The current release contains information on 25,101 DEGs representing 14,320 unique rat genes that change transcription levels in 21 tissues of 10 genetic rat strains used as models of 11 human diseases based on 45 original scientific papers. RatDEGdb is novel in that, unlike any other biomedical database, it offers the manually curated annotations of DEGs in model rats with the use of independent clinical data on equal changes in the expression of homologous genes revealed in people with pathologies. The rat DEGs put in RatDEGdb were annotated with equal changes in the expression of their human homologs in affected people. In its current release, RatDEGdb contains 94,873 such annotations for 321 human genes in 836 diseases based on 959 original scientific papers found in the current PubMed. RatDEGdb may be interesting first of all to human geneticists, molecular biologists, clinical physicians, genetic advisors as well as experts in biopharmaceutics, bioinformatics and personalized genomics. RatDEGdb is publicly available at https://www.sysbio.ru/RatDEGdb.

Social behavior and spatial orientation in rat strains with genetic predisposition to catatonia (GC) and stereotypes (PM).

Various psychopathologies, including schizophrenia, bipolar disorder and major depression, are associated with abnormalities in social behavior and learning. One of the syndromes that may also take place in these disorders is catatonia. Catatonia is a psychomotor syndrome in which motor excitement, stereotypy, stuporous state, including the phenomenon of "waxy flexibility" (catalepsy), can be observed. Rats with genetic catatonia (GC) and pendulum-like movements (PM) of the anterior half of the body have physiological and behavioral changes similar to those observed in schizophrenia and depression in humans and can be considered as incomplete experimental models of these pathologies. The social behavior of the GC and PM rats has not been previously studied, and the cognitive abilities of animals of these strains are also insufficiently studied. To determine whether the GC and PM rats have changes in social behavior and spatial learning, behavioral phenotyping was performed in the resident-intruder test, three-chamber test, Barnes maze test. Some deviations in social behavior, such as increased offensive aggression in PM rats in the resident-intruder test, increased or decreased social interactions depending on the environment in different tests in GC, were shown. In addition, principal component analysis revealed a negative association between catatonic freezing and the socialization index in the three-chamber test. Decreased locomotor activity of GС rats can adversely affect the performance of tasks on spatial memory. It has been shown that PM rats do not use a spatial strategy in the Barnes maze, which may indicate impairment of learning and spatial memory.

Antisense Oligonucleotides Immobilized on Silicon-Organic Nanoparticles as a Tool for Prolonged Correction of Hypertensive States.

We propose an original method for controlling BP by administration of Si~ODN nanocomposites containing antisense oligonucleotides fixed on silicon-organic nanoparticles. ODN in nanocomposites are targeted to mRNA of the genes encoding angiotensin-converting enzyme (ACE1) and type 1 angiotensin-II receptor (AT1A). The experiments were performed on hypertensive ISIAH rats, a genetic model of hypertension. Single inhalation or intraperitoneal administration of the nanocomposites targeted to ACE1 mRNA or ATA1 mRNA, respectively, led to a pronounced decrease (by ~30 mm Hg) in systolic BP in ISIAH rats over a week. The use of scrambled ODN in the nanocomposites had no effect. A decrease in the expression of ACE1 and AT1A genes under the effect of the corresponding antisense ODN was demonstrated, which attested to directed effect of the test preparations.

[Increase in the concentration of sEH protein in renal medulla of ISIAH rats with inherited stress-induced arterial hypertension].

The concentration of soluble epoxide hydrolase (sEH) protein was studied in renal medulla of adult rats from hypertensive ISIAH strain and normotensive WAG strain. The sEH is a key enzyme in metabolism of epoxyeicosatrienoic acids capable of activating endothelial NO-synthase and nitrogen oxide formation, and therefore being vasodilators. An increase in the sEH protein concentration (that we found) allows one to assume that the oxidative stress is increased in the renal medulla of hypertensive rats, and the bloodflow is decreased.

Expression of renin-angiotensin system genes in brain structures of ISIAH rats with stress-induced arterial hypertension.

We studied the expression of genes encoding angiotensinogen (Agt), renin (Ren), angiotensin-converting enzyme (ACE), and type 1 angiotensin receptor (AT1A) in the hypothalamus and medulla oblongata of hypertensive ISIAH rats and normotensive WAG rats. The amount of Agt mRNA in the hypothalamus of young ISIAH rats was increased by 30% compared to WAG controls. In the medulla oblongata of young ISIAH rats, the levels of mRNA of Agt and AT1A receptor were enhanced by 60% and 24%, respectively, compared to WAG rats. In adult animals, the expression of the studied genes did not differ from the control. It is concluded that changes in gene expression of the renin-angiotensin system in brain structures of ISIAH rats may contribute to the development of hypertension.

Gene expression for the renin system in the myocardium of hypertensive ISIAH rats.

The concentration of mRNA for angiotensin-converting enzyme (ACE) and angiotensin type 1A receptor (AT1A) in the myocardium of hypertensive ISIAH rats and normotensive WAG rats was measured by real-time PCR. Gene expression of the angiotensin type 1A receptor in the myocardium of 4-month-old ISIAH rats was lower than in WAG rats. The content of mRNA for angiotensin-converting enzyme in the myocardium of adult ISIAH rats was elevated by 80%. Therefore, the development of myocardial hypertrophy anticipates the increase in enzyme expression in the myocardium. Water deprivation (17 h) was accompanied by a decrease in the concentration of mRNA for angiotensin-converting enzyme in the myocardium of ISIAH rats, which did not differ from that in normotensive animals. Our results suggest that the decrease in cardiac preload and increase in plasma renin activity during dehydration reduce requirements for hyperactivity of the local cardiac renin-angiotensin system.