Whole genome sequencing of nearly isogeneic WMI and WLI inbred rats identifies genes potentially involved in depression

BackgroundThe WMI and WLI inbred rat substrains were generated from the stress-prone, and not yet fully inbred, Wistar Kyoto (WKY) strain using bi-directional selection for immobility in the forced swim test followed by over 38 generations of inbreeding. Despite the low level of genetic diversity among WKY progenitors, the WMI substrain is more vulnerable to stress relative to its WLI control substrain. Here we quantify numbers and classes of sequence variants distinguishing these substrains and test the hypothesis that they are nearly isogenic. Results: The WLI and WMI genomic DNA were sequenced using Illumina xTen, IonTorrent and 10X Chromium technologies to obtain a combined coverage of over 100X. We identified 4,296 high quality homozygous SNPs and indels that differ between the WMI and WLI substrains. Gene ontology analysis of these variants showed an enrichment for neurogenesis related pathways. In addition, high impact variations were detected in genes previously implicated in depression (e.g. Gnat2), depression-like behavior (e.g. Prlr, Nlrp1a), other psychiatric disease (e.g. Pou6f2, Kdm5a, Reep3, Wdfy3) or stress response (e.g. Pigr).ConclusionsThe high coverage sequencing data confirms the near isogenic nature of the two substrains, which combined with the variants detected can lead to the identification of genetic factors underlying greater susceptibility for depression, stress reactivity, and addiction.

Comparative effectiveness of Molixan and Glutoxim in the model of toxic liver lesions with anti-tuberculosis drugs

Due to the high frequency of liver lesions caused by anti-tuberculosis drugs, the possibility of using compounds based on oxidized glutathione for hepatoprotection is shown. Purposes and tasks. The purpose of the study was to conduct a comparative assessment of the hepatoprotective properties of molixan and glutoxim in liver lesions with anti-tuberculosis drugs. To achieve this goal, it was necessary to perform the following tasks: on the model of toxic liver damage caused by anti-tuberculosis drugs (isoniazid, rifampicin, pyrazinamide) to study the effectiveness of glutoxin and molixan by biochemical and morphological parameters; on the basis of the data to determine the most effective scheme of application. Materials and methods: the study was conducted on 90 white male not inbred rats. Antituberculosis drugs (AD) were administered to animals daily for 14 days in the following doses: isoniazid – 50 mg/kg intraperitoneal, rifampicin – 250 mg/kg and pyrazinamide – 45 mg/kg intragastrically. Glutoxim and molixan were administered daily for 14 days at doses: 20 and 40 mg/kg – glutoxim, 30 mg/kg – molixan, intraperitoneal for 2 hours before the introduction of anti-tuberculosis drugs. The animals were divided into 5 groups of 18 rats each. Group 1 – intact animals, 2 – control AD, 3 – AD + glutoxim 20 mg/kg, 4 – AD + glutoxim 40 mg/kg, 5 – AD + molixan 30 mg/kg. In the study on day 15, biochemical parameters of blood were determined, the liver was taken for morphohistological study and the level of LPO in its homogenates was determined by the concentration of diene conjugates and malondialdehyde. Results and conclusions. As a result of the experimental study, it was noted that the more pronounced hepatoprotective effect was exerted by molixan.

The role of central and peripheral D2R receptors in the mechanism of colonic vascular permeability during experimental colitis in rats

We investigated the involvement of central and peripheral D2 dopaminergic receptors in the mechanism of vascular permeability in rat's colon during experimental ulcerative colitis. Ulcerative colitis was induced in male white inbred rats by 6 % iodoacetamide enema. For the investigation of central and peripheral D2R, separate and joint injections of D2R antagonist domperidone (2 mg/100 g, per os) and D2R agonist quinpirole (1 mg/100 g, per os) were applied. Central D2R were destroyed by neurotoxin injection – 6OHDA. Colonic vascular permeability was measured by colonic extravasation of 1,5 % Evans blue. It was observed that blockade of peripheral D2R decreased colonic vascular permeability, while simultaneous activation of central D2R and inhibition of peripheral D2R have additive positive effect in prevention of increased colonic vascular permeability during experimental colitis.

ENTEROSORPTION COMBINED WITH GRANULOCYTE COLONY STIMULATING FACTOR DECREASES MELPHALAN GONADAL TOXICITY

Today due to improvements in cancer treatment there is an increasing number of long-term cancer survivors, many of whom suffer from infertility caused by malignancy itself and chemo- or radiotherapy. Also, anticancer therapy may cause myelosuppression. Presently granulocyte colony stimulating factor (G-CSF) is used for prevention and treatment of myelosuppression. Another treatment option used to decrease intoxication and ameliorate side effects of cancer therapy is sorption technology. The aim of our investigation was to study the efficiency of combined use of enterosorption and G-CSF to decrease gonadal toxicity of chemotherapy. Materials and Methods: Melphalan (L-PAM) injected i.v. at a single dose of 4 mg/kg to white inbred rats was used as gonadotoxic and myelosuppressing agent. Carbon enterosorbent C2 was administered by intragastric route as a suspension in saline at a dose of 5 ml per 1 kg of rats’ body weight (or 900 mg/kg of the dry mass of enterosorbent) daily for 3 days before and for 7 days after L-PAM injection. G-CSF was injected once a day for 4 days starting from the next day after L-PAM administration at a dose of 50 µg/kg. Histological preparations of testicular tissues were examined by light microscopy. Results: Our findings have shown that melphalan caused marked damage of testicular tissues and seminiferous, especially spermatogenic epithelium. The most expressed protection of the histological structure of testes was observed when enterosorbent and G-CSF were used in combination. Conclusion: Gonadal toxicity of chemotherapy could be efficiently decreased by the combined use of enterosorption and G-CSF.