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Project description:The Göttingen Minipig is gaining ground as nonrodent species in safety testing of drugs for pediatric indications. Due to developmental changes in pharmacokinetics (PK) and pharmacodynamics (PD), physiologically-based pharmacokinetic (PBPK) models are built to better predict drug exposure in children and to aid species selection for nonclinical safety studies. These PBPK models require high quality physiological and PK/PD data such as protein abundance of drug metabolizing enzymes. These data are available for man and rat, but scarce for the Göttingen Minipig. The aim of this study was to assess hepatic cytochrome P450 (CYP) protein abundance in the developing Göttingen Minipig by using mass spectrometry. In addition, sex-related differences in CYP protein abundance and correlation of CYP enzyme activity with CYP protein abundance were assessed. The following age groups were included: gestational day (GD) 84 - 86 (n = 8), GD 108 (n = 6), postnatal day (PND) 1 (n = 8), PND 3 (n = 8), PND 7 (n = 8), PND 28 (n = 8) and adult (n = 8). Liver microsomes were extracted and protein abundance was compared to that in adult animals. Next, the CYP protein abundance was correlated to CYP enzyme activity in the same biological samples. In general, CYP protein abundance gradually increased during development. However, we observed a stable protein expression over time for CYP4A24 and CYP20A1 and for CYP51A1, a high protein expression during the fetal stages was followed by a decrease during the first month of life and an increase towards adulthood. Sex-related differences were observed for CYP4V2_2a and CYP20A1 at PND 1 with highest expression in females for both isoforms. In the adult samples, sex-related differences were detected for CYP1A1, CYP1A2, CYP2A19, CYP2E1_2, CYP3A22, CYP4V2_2a and CYP4V2_2b with higher values in female compared to male Göttingen Minipigs. The correlation analysis between CYP protein abundance and CYP enzyme activity showed that CYP3A22 protein abundance correlated clearly with the metabolism of midazolam at PND 7. These data are remarkably comparable to human data and provide a valuable step forward in the construction of a neonatal and juvenile Göttingen Minipig PBPK model.
2021-02-26 | PXD024158 | Pride
Project description:Age- and lactocrine-sensitive elements of the neonatal porcine uterine developmental program are undefined. Here, effects of age and nursing for 48 h from birth (postnatal day = [PND] 0) on the uterine transcriptome at PND 2 were identified using RNA sequencing. Pig uterine tissues were obtained from neonatal gilts (n = 4/group) within 1 h of birth [postnatal day (PND) 0], or 48 h after nursing ad libitum (PND 2N), or feeding a commercial milk replacer (PND 2R).
2016-02-15 | E-GEOD-72388 | biostudies-arrayexpress
Project description:Postoperative neurocognitive disorder (PND) is one of the most common postoperative neurological complications in aged patients. In order to detect the differential expression profiles of genes caused by PND, a total of 26 18-month-old male C57BL/6 mice were randomly assigned to control group and PND group. Behavioral tests showed that mice in the PND group had impaired cognitive function compared with the control group. Three mice in each group were randomly selected to harvest the brain for analysis the expressions of circRNAs, miRNAs and mRNAs in the prefrontal cortex by next-generation sequencing (NGS) technology. Differentially expressed genes, including 1192 circRNAs, 27 miRNAs and 266 mRNAs were identified, and its accuracy was further confirmed by qRT-PCR.
2021-06-23 | GSE174411 | GEO
Project description:Postoperative neurocognitive disorder (PND) is one of the most common postoperative neurological complications in aged patients. In order to detect the differential expression profiles of genes caused by PND, a total of 26 18-month-old male C57BL/6 mice were randomly assigned to control group and PND group. Behavioral tests showed that mice in the PND group had impaired cognitive function compared with the control group. Three mice in each group were randomly selected to harvest the brain for analysis the expressions of circRNAs, miRNAs and mRNAs in the prefrontal cortex by next-generation sequencing (NGS) technology. Differentially expressed genes, including 1192 circRNAs, 27 miRNAs and 266 mRNAs were identified, and its accuracy was further confirmed by qRT-PCR.
2021-06-23 | GSE174410 | GEO
Project description:Perioperative neurocognitive dysfunction (PND) is emerging as a significant complication of surgery in elderly patients. However, the molecular mechanisms of PND are not well known. Here we applied microarray analysis to identify circular RNAs (circRNAs) in hippocampus from a mouse model of PND and control mice. Then, the dysregulated circRNAs were confirmed via quantitative real-time polymerase chain reaction (qRT-PCR). Then, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to probe the vital functions of dysregulated genes.
2021-08-10 | GSE165798 | GEO
Project description:Background: Perioperative neurocognitive disorders (PND), a postoperative cognitive dysfunction occurs more often in the elderly. The etiology of PND remains largely elusive. This study aims to understand the etiology in a mouse model with tibial fracture (a surgical trauma), by examining the transcriptome-wide response of hippocampus, a brain region that is tightly associated with memory formation. Methods: Mice at age of 7~8 months were randomly divided into two groups, surgery (tibial fracture) group and control (sham) group. At day (d) 1 after the surgical operation, hippocampal tissues were isolated and then subjected to RNA extraction and RNA sequencing (RNA-seq). Findings: Levels of respiratory complex related genes are significantly decreased in the brain of mice subjected to surgery. Consequently, the activities of multiple respiratory complexes and respiratory chain function is decreased in the hippocampus of mice with surgical operation. Interpretation: We here propose a novel mechanism of mitochondrial dysfunction in PND etiology, and also provide a potential therapeutic target for PND.
2022-02-09 | GSE178995 | GEO