Project description:Short day (8hrs of light/day) housed juvenile, male F344 rats were injected with 10^-5 M all-trans RA or vehicle (saline) into the third ventricle of the hypothalamus. 24 hours after RA injections rats were killed by decapitation after isoflurane inhalation at ZT3 and brains were dissected and frozen on dry ice. Hypothalamic arcuate nucleus tissue blocks were cut for RNA exaction. 4 rats per group were used giving 8 rats in total.
Project description:F344 rats were divided into 4 groups: vehicle control, DEN, DEN+CLO and CLO. After one week of basal diet, rats belonging to the groups DEN and DEN+CLO underwent intraperitoneal injection of DEN (30mg/kg body weight) dissolved in NaCl 9‰. The two other groups were injected with NaCl 9‰ alone. At 30mg/kg, DEN is non-necrogenic thus only exhibiting initiating properties. Twelve days after injection, diet from rats belonging to the groups CLO and DEN+CLO was changed for diet containing 5000ppm CLO for up to 608 days. Series of 5 rats from each group were necropsied at days 18, 46, 102, 264, 377, 447 (reverse phase from day 377: no more CLO in the diet for rats belonging to the DEN+CLO group), and for the CLO and Control group 524, and 608 days after the injection of DEN or saline. From day 524, half of the CLO-treated rats were kept on basal diet (reverse phase) until day 608. Keywords = Clofibric acid Keywords = Diethylnitrosamine Keywords = Rat Keywords: other
Project description:NAP - neuroprotective peptide demonstrates increase in neuronal survival when injected into the hippocampus of rats in the model of epilepsy Microarray analysis was used to understand the expression of genes following KA treatment and the changes in gene expression following KA+NAP treatment Keywords: stress response KA was injected into the hippocampus of Sprague-Dawley rats. The other group of rats was injected with KA and NAP(10-13M). The third group was injected with NAP only and the last group was injected with PBS as a vehicle. CA3 area of hippocampus was removed 24h later and RNA extraction was done. The samples were subjected to microarray analysis.
Project description:Aging is associated with low-grade chronic systemic inflammation. Elevated peripheral serum cytokines and chemokines contribute to age-related diseases and correlate with cognitive decline. This study compared the effects of repeated lipopolysaccharide (LPS) treatment in young rats to age-related changes in hippocampal-dependent cognition, synaptic transmission, and transcription. Young (5-7 months) Fischer 344 X Brown Norway hybrid rats were injected intraperitoneally once a week for 6-7 weeks with either LPS (1 mg/kg) or vehicle. Older (14-16 months) rats received a similar injection schedule of vehicle. Older-vehicle animals and young-LPS rats exhibited impaired retention of spatial memory. Examination of the transcriptome of the CA1 and the dentate gyrus indicated that older-vehicle and young-LPS animals exhibited an increase in immune response genes. In contrast to aging, young-LPS animals exhibited an increased expression of genes related to the synapse. Even though young-LPS animals increased the expression of synaptic genes, LPS treatment reduced hippocampal CA3-CA1 total synaptic response and N-methyl-D-aspartate receptor (NMDAR)-mediated component of the synaptic response. Interestingly, the decrease in NMDAR function was not redox-sensitive. This study demonstrates that repeated exposure to LPS has long-term effects on hippocampal synaptic transmission and memory; however, young animals exhibited transcriptional recovery after LPS treatment. Recovery likely results from the acute nature of repeated LPS injections, relative to chronic systemic inflammation observed during aging.
Project description:Progesterone (P4) acting through its cognate receptor, the progesterone receptor (PR), plays an important role in uterine physiology. The PR knockout (PRKO) mouse has demonstrated the importance of the P4-PR axis in the regulation of uterine function. To define the molecular pathways regulated by P4-PR in the mouse uterus, Affymetrix MG U74Av2 oligonucleotide arrays were used to identify alterations in gene expression after acute and chronic P4 treatments. In the analysis, retinoic acid metabolic genes, cytochrome P 450 26a1 (Cyp26a1), alcohol dehydrogenase 5, and aldehyde dehydrogenase 1a1 (Aldh1a1); kallikrein genes, Klk5 and Klk6; and specific transcription factors, GATA-2 and Cited2 [cAMP-corticosterone-binding protein/p300-interacting transactivator with glutamic acid (E) and aspartic acid (D)-rich tail], were validated as regulated by the P4-PR axis. Identification and analysis of these responsive genes will help define the role of PR in regulating uterine biology. Ovariectomized wild-type and progesterone receptor knockout mice were injected with either vehicle or 1 mg/mouse progesterone. The injections were repeated every 12 h, and groups of mice were killed 4 h after the first injection (acute P4 treatment) or 4 h after the fourth injection (chronic P4 treatment).
Project description:F344 rats were divided into 4 groups: vehicle control, DEN, DEN+CLO and CLO. After one week of basal diet, rats belonging to the groups DEN and DEN+CLO underwent intraperitoneal injection of DEN (30mg/kg body weight) dissolved in NaCl 9â°. The two other groups were injected with NaCl 9â° alone. At 30mg/kg, DEN is non-necrogenic thus only exhibiting initiating properties. Twelve days after injection, diet from rats belonging to the groups CLO and DEN+CLO was changed for diet containing 5000ppm CLO for up to 608 days. Series of 5 rats from each group were necropsied at days 18, 46, 102, 264, 377, 447 (reverse phase from day 377: no more CLO in the diet for rats belonging to the DEN+CLO group), and for the CLO and Control group 524, and 608 days after the injection of DEN or saline. From day 524, half of the CLO-treated rats were kept on basal diet (reverse phase) until day 608.
Project description:The aim of reprotoxicity testing is to reveal adverse effects of chemicals and drugs on reproduction and on pre and postnatal fetal development. There is very limited data available on gene expression profiling for elucidation of the teratogenic effects of nongenotoxic teratogens. Therefore, research was undertaken to obtain knowledge on the molecular effects of MSC1096199 (previously known as EMD 82571), a calcium sensitizer that was abandoned in the preclinical development phase due to its teratogenic effects in some foetuses. Pregnant wistar rats were dose daily with either MSC1096199 (50 or 150 mg/kg) or Retinoic acid (10 mg/kg) on gestational days 6-17. Microarray experiment were performed using four different tissues (maternal liver, embryo liver (GD20), embryo bone (GD20), and whole embryo (GD12)) under four different conditions (vehicle, low dose and high dose of MSC1096199 and Retinoic acid) to determine the drug regulated genes. In the high dose treatment group, approximately 58% of the fetuses showed malformations i.e. exencephaly and agnathia, and toxicogenomics evidenced that the genes critically involved in osteogenesis, odontogenesis and extra cellular matrix components to be significantly regulated by MSC1096199, therefore providing a molecular rational for the observed teratogenic effects. Pregnant wistar rats were treated daily with the dose of either MSC1096199 (50 or 150 mg/kg) or Retinoic acid (10 mg/kg) on gestational days 6-17. Microarray experiment were performed using four different tissues (maternal liver, embryo liver, embryo bone, and whole embryo) under four different conditions (vehicle, low dose and high dose of MSC1096199 and Retinoic acid) to determine the drug regulated genes.