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: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: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: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:A recent two-year NTP cancer bioassay showed a marked increase in the incidence of malignant mesothelioma arising from the tunica vaginalis in male Fischer 344/N rats exposed to Vinylidene chloride (VDC). Aged male F344/N rats are prone to developing spontaneous peritoneal mesotheliomas, which also arise predominantly from the tunica vaginalis of the testes. A definitive mechanism for the observed increased incidence in VDC-exposed rats is unknown. Investigation of the molecular alterations that occur in mesotheliomas from vehicle control and VDC-exposed rats may provide insight into their pathogenesis, as well enable a better understanding regarding the mechanisms underlying chemically induced mesothelioma in rodents. Mesothelial cell function represents a complex interplay of pathways related to host defense mechanisms and maintenance of cellular homeostasis. Global gene expression profiles of spontaneous mesotheliomas from vehicle control male F344/N rats from various two-year National Toxicology Program carcinogenicity bioassays were compared to mesotheliomas from VDC-exposed rats to characterize the molecular features that are present in mesotheliomas from VDC-exposed animals, and to elucidate tumor-specific gene expression profiles. The resulting gene expression pattern showed that mesotheliomas from VDC-exposed animals are genomically very different from spontaneous tumors; while both tumor types are characterized by alterations in gene expression associated with carcinogenic pathways (oncogenes, tumor suppressor genes, growth factors, etc.), mesotheliomas from VDC-exposed animals are associated with increased dysreguation of immune pathways and inflammatory mediators. Alterations in these pathways may suggest a pro-inflammatory and immune dysfunction signature as one mechanism in the observed increased incidence of these tumors in VDC-exposed animals.