Sex differences in cardiac aging in mice and development of a female murine model of hypertensive disease in the elderly
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ABSTRACT: C57Bl6/J male and female mice were gonadectomized or not at the age of 12 months and then euthanized 12 months later at the age of 24 months. Half of the females received for 28 days an angiotensin II (AngII; 1.5 mg/kg/day) continuous infusion starting at the age of 23 months. The mice were provided with a running wheel during the 12 months after gonadectomy with the exception of the last month before euthanasia.
Project description:C57Bl6/J female mice were ovariectomized or not at the age of 12 months and then euthanized 12 months later at the age of 24 months. Half of the females received for 28 days an angiotensin II (AngII; 1.5 mg/kg/day) continuous infusion starting at the age of 23 months. The mice were provided with a running wheel during the 12 months after gonadectomy with the exception of the last month before euthanasia.
Project description:In order to study the capacity of the myocardium to recover from a stress causing several features of heart failure with preserved ejection fraction, C57Bl6/J male and female mice received or not for 28 days an angiotensin II (AngII; 1,5 mg/kg/day) continuous infusion in combination with a high fat diet (HFD). Half of the animals were then euthanized. The remaining ones had the AngII infusion stopped and their diet normalized. In addition, voluntary exercise was initiated by introducing a running wheel in the animals cage for an additional 28 days.
Project description:Dahl-Iwai (DI) salt-sensitive rats were studied using microarrays to identify gender-specific differences in the kidney, both basal differences and responses to a high salt diet. In DI rat kidneys, gene expression profiles demonstrated inflammatory and fibrotic responses selectively in females. Gonadectomy of DI rats abrogated gender differences in gene expression. Gonadectomized female and gonadectomized male DI rats both responded to high salt with the same spectrum of gene expression changes as intact female DI rats. Androgens dominated the gender selective responses to salt. Several androgen-responsive genes were identified with roles potentiating the differential responses to salt including increased male expression of Angiotensin-Vasopressin Receptor and Prolactin Receptor, decreased 5-alpha reductase, and mixed increases and decreases in expression of Cyp4a- genes that can produce eicosanoid hormones. These gender differences potentiate sodium retention by males, and increase kidney function during gestation by females. Keywords: Disease-State Analysis (Salt-Sensitive Hypertension)
Project description:Aim of the experiment was to study the role of gonadectomy and testosterone treatment on liver gene expression of male mice. Gonadectomized male mice received infusion of testosterone or vehicle, and liver was used to perform RNAseq analysis.
Project description:Gonadectomy (GDX) induces sex steroid-producing adrenocortical tumors in certain mouse strains and in the domestic ferret. Complementary approaches, including DNA methylation mapping and microarray expression profiling, were used to identify novel genetic and epigenetic markers of GDX-induced adrenocortical neoplasia in female DBA/2J mice. Markers were validated by quantitative RT-PCR, laser capture microdissection, in situ hybridization, and immunohistochemistry. Two genes with hypomethylated promoters, Igfbp6 and Foxs1, were upregulated in post-GDX adrenocortical neoplasms. The neoplastic cells also exhibited hypomethylation of the fetal adrenal enhancer of Sf1, an epigenetic signature that typifies descendants of fetal adrenal rather than gonadal cells. Expression profiling demonstrated upregulation of gonadal-like genes, including Spinlw1, Insl3, and Foxl2, in GDX-induced adrenocortical tumors of the mouse. One of these markers, FOXL2, was detected in adrenocortical tumor specimens from gonadectomized ferrets. These new markers may prove useful for studies of steroidogenic cell development and for diagnostic testing. Total RNA extracted from whole adrenal glands of gonadectomized and non-gonadectomized mice.
Project description:To understand the sex differences in brain function that underlie sex differences in behavior we measured the transcriptome of POM, VMN and TnA of adult quail of both sexes either left gonadally intact or gonadectomized and treated with testosterone. Gonadectomy and testosterone-treated groups allowed us to distinguish a suite of genes whose expression is sensitive to testosterone and a suite of genes that are not, the magnitude and pattern of which differs by sex and nucleus.
Project description:Both aging and physical activity can influence the amount of connective tissue in skeletal muscle, but the impact of these upon specific extracellular matrix (ECM) proteins in skeletal muscle is unknown. We investigated the proteome profile of connective tissue in skeletal muscle by label-free proteomic analysis of on cellular protein-depleted extracts from lateral gastrocnemius muscle of old (22-23 months old) and middle-aged mice (11 months old) subjected to three different levels of regular physical activity for 10 weeks (high resistance wheel running, low resistance wheel running or sedentary controls). We hypothesized that aging is correlated with increased amount of connective tissue proteins in skeletal muscle, and that regular physical activity can counteract these age-related changes. We found that dominating cellular proteins were diminished in the urea/thiourea extract, which was therefore used for proteomics. Proteomic analysis identified 482 proteins and showed enrichment for ECM proteins. Statistical analysis revealed that the abundances of 86 proteins were changed with age. Twenty-three of these differentially abundant proteins were identified as structural ECM proteins (e.g., collagens and laminins) and all of these were significantly more abundant with aging. No significant effect of training or interaction between training and advance in age was found for any proteins. Finally, we found a lower protein concentration in the urea/thiourea extracts from the old compared to middle-aged mice. These findings indicate that intramuscular connective tissue alters its protein content with age but is unaffected by training.
Project description:Liver are frequently declined for transplantation due to the donor age. It is still unclear how donor age affects the graft quality. Normothermic machine perfusion (NMP) has been proposed as a useful assessment tool prior to transplantation. We aimed to compare the performance of young and elderly rat liver grafts in a small animal NMP model. Grafts from 24 rats were procured, either 3 or 12 months old and perfused for 6 hours at 37°C or stored on ice as a reference group (n=6/group). Livers in both NMP groups cleared lactate and produced bile, with similar pressure, bile production, and pH levels. However, older rat livers showed higher peak transaminase and urea levels. Proteomic analysis revealed differences in protein composition, particularly higher levels of proteins related to oxidoreductase and catalytic activity in older livers. Older age appeared to increase susceptibility to oxidative stress in the livers.
Project description:This analysis was done to determine which muscle group has the most skeletal muscle transcriptional reponses to wheel running activity. Seven male mice with C57BL/6 genetic background were placed individually in cages with running wheels and allowed free access to the wheels 24 hr per day. Access to running wheels began when the mice were 6 months old, and continued for 12 weeks. The morning after the night of running, the mice were euthanized and several muscle groups were snap froze in liquid nitrogen to preserve RNA. The same muscle groups were collected from three age-matched "sedentary" mice that were housed in ordinary cages that did not permit sustained running. For each muscle group, separate pools of polyadenylated RNA from the sedentary and wheel-running mice were prepared for deep sequencing of cDNA with the SOLiD 3 platform.
Project description:This analysis was done to determine which muscle group has the most skeletal muscle transcriptional reponses to wheel running activity. Seven male mice with C57BL/6 genetic background were placed individually in cages with running wheels and allowed free access to the wheels 24 hr per day. Access to running wheels began when the mice were 6 months old, and continued for 12 weeks. The morning after the night of running, the mice were euthanized and several muscle groups were snap froze in liquid nitrogen to preserve RNA. The same muscle groups were collected from three age-matched "sedentary" mice that were housed in ordinary cages that did not permit sustained running. For each muscle group, separate pools of polyadenylated RNA from the sedentary and wheel-running mice were prepared for deep sequencing of cDNA with the SOLiD 3 platform. Four muscle groups were examined (quadriceps femoris; gastrocnemius/plantaris; tibialis anterior; triceps brachii). For each muscle, RNA was pooled from 3 sedentary or 7 wheel-running mice (8 pools total).