Search results for "Knockout"
showing 10 items of 806 documents
Adipocyte cannabinoid CB1 receptor deficiency alleviates high fat diet-induced memory deficit, depressive-like behavior, neuroinflammation and impair…
2019
Abstract Background Obesity is a low-grade inflammation condition that facilitates the development of numerous comorbidities and the dysregulation of brain homeostasis. Additionally, obesity also causes distinct behavioral alterations both in humans and rodents. Here, we investigated the effect of inducible genetic deletion of the cannabinoid type 1 receptor (CB1) in adipocytes (Ati-CB1-KO mice) on obesity-induced memory deficits, depressive-like behavior, neuroinflammation and adult neurogenesis. Methods Behavioral, mRNA expression and immunohistochemical studies were performed in Ati-CB1-KO mice and corresponding wild-type controls under standard and high-fat diet. Results Adipocyte-speci…
Antidepressant-like behavioral effects of impaired cannabinoid receptor type 1 signaling coincide with exaggerated corticosterone secretion in mice.
2007
Hypothalamic-pituitary-adrenocortical (HPA) axis hyperactivity is associated with major depressive disorders, and treatment with classical antidepressants ameliorates not only psychopathological symptoms, but also the dysregulation of the HPA axis. Here, we further elucidated the role of impaired cannabinoid type 1 receptor (CB1) signaling for neuroendocrine and behavioral stress coping in the mouse forced swim test (FST). We demonstrate that the genetic inactivation of CB1 is accompanied by increased plasma corticosterone levels both under basal conditions and at different time points following exposure to the FST. The latter effect could be mimicked in C57BL/6N mice by acute, subchronic, …
Effect of circulating growth hormone on muscle IGF-I protein concentration in female mice with growth hormone receptor gene disruption.
2009
Growth hormone (GH) is a potent secretague for circulating insulin-like growth factor-I (IGF-I). The purpose of this study was to examine the effect of circulating GH on muscle IGF-I protein expression using GH transgenic animal models. Three different models were used: mice that overexpress bovine GH (bGH; n=10), mice without a functional GH receptor (GHR-/-; n=10), and wildtype mice (n=10). All mice were 16-week old females and each group differed in their basic phenotypic characteristics. Immediately after euthanization the triceps surae muscle group (soleus, plantaris, and gastrocnemius muscles) was removed. IGF-I was extracted from the muscle with an acid-ethanol solution (12.5% 2N hyd…
Low Protein Intake Is Associated with a Major Reduction in IGF-1, Cancer, and Overall Mortality in the 65 and Younger but Not Older Population
2014
SummaryMice and humans with growth hormone receptor/IGF-1 deficiencies display major reductions in age-related diseases. Because protein restriction reduces GHR-IGF-1 activity, we examined links between protein intake and mortality. Respondents aged 50–65 reporting high protein intake had a 75% increase in overall mortality and a 4-fold increase in cancer death risk during the following 18 years. These associations were either abolished or attenuated if the proteins were plant derived. Conversely, high protein intake was associated with reduced cancer and overall mortality in respondents over 65, but a 5-fold increase in diabetes mortality across all ages. Mouse studies confirmed the effect…
Sex differences in nucleus accumbens transcriptome profiles associated with susceptibility versus resilience to subchronic variable stress
2015
Depression and anxiety disorders are more prevalent in females, but the majority of research in animal models, the first step in finding new treatments, has focused predominantly on males. Here we report that exposure to subchronic variable stress (SCVS) induces depression-associated behaviors in female mice, whereas males are resilient as they do not develop these behavioral abnormalities. In concert with these different behavioral responses, transcriptional analysis of nucleus accumbens (NAc), a major brain reward region, by use of RNA sequencing (RNA-seq) revealed markedly different patterns of stress regulation of gene expression between the sexes. Among the genes displaying sex differe…
Regulation of Oxygen Distribution in Tissues by Endothelial Nitric Oxide
2009
Nitric oxide (NO) decreases cellular oxygen (O 2 ) consumption by competitively inhibiting cytochrome c oxidase. Here, we show that endogenously released endothelial NO, either basal or stimulated, can modulate O 2 consumption both throughout the thickness of conductance vessels and in the microcirculation. Furthermore, we have shown that such modulation regulates O 2 distribution to the surrounding tissues. We have demonstrated these effects by measuring O 2 consumption in blood vessels in a hypoxic chamber and O 2 distribution in the microcirculation using the fluorescent oxygen-probe Ru(phen) 3 2+ . Removal of NO by physical or pharmacological means, or in eNOS −/− mice, abolishes this …
Chronic Therapy With Isosorbide-5-Mononitrate Causes Endothelial Dysfunction, Oxidative Stress and a Marked Increase in Vascular Endothelin-1 Express…
2011
Aims Isosorbide-5-mononitrate (ISMN) is one of the most frequently used compounds in the treatment of coronary artery disease predominantly in the USA. However, ISMN was reported to induce endothelial dysfunction, which was corrected by vitamin C pointing to a crucial role of reactive oxygen species (ROS) in causing this phenomenon. We sought to elucidate the mechanism how ISMN causes endothelial dysfunction and oxidative stress in vascular tissue. Methods and results Male Wistar rats ( n = 69 in total) were treated with ISMN (75 mg/kg/day) or placebo for 7 days. Endothelin (ET) expression was determined by immunohistochemistry in aortic sections. Isosorbide-5-mononitrate infusion caused si…
Modulation by NO of acetylcholine release in the ileum of wild-type and NOS gene knockout mice.
2002
Nitric oxide (NO) inhibits the release of acetylcholine and cholinergic contractions in the small intestine of several species, but no information is available about the mouse ileum. This study examines the effects of NO on the electrically evoked release of [3H]acetylcholine and smooth muscle contraction in myenteric plexus-longitudinal muscle preparations of wild-type mice and of neuronal NO synthase (nNOS) and endothelial NOS (eNOS) knockout mice. The NOS inhibitor N G-nitro-l-arginine (l-NNA) and the guanylyl cyclase inhibitor 1 H-[1,2,4]oxadiazolo[4,3-α]quinoxalin-1-one (ODQ) concentration dependently increased the evoked [3H]acetylcholine release and cholinergic contractions in prepa…
Resveratrol Reverses Endothelial Nitric-Oxide Synthase Uncoupling in Apolipoprotein E Knockout Mice
2010
A crucial cause of the decreased bioactivity of nitric oxide (NO) in cardiovascular diseases is the uncoupling of the endothelial NO synthase (eNOS) caused by the oxidative stress-mediated deficiency of the NOS cofactor tetrahydrobiopterin (BH(4)). The reversal of eNOS uncoupling might represent a novel therapeutic approach. The treatment of apolipoprotein E knockout (ApoE-KO) mice with resveratrol resulted in the up-regulation of superoxide dismutase (SOD) isoforms (SOD1-SOD3), glutathione peroxidase 1 (GPx1), and catalase and the down-regulation of NADPH oxidases NOX2 and NOX4 in the hearts of ApoE-KO mice. This was associated with reductions in superoxide, 3-nitrotyrosine, and malondiald…
Oxytocin Regulates Neurosteroid Modulation of GABAAReceptors in Supraoptic Nucleus around Parturition
2003
In this study, we investigate how neurosteroid sensitivity of GABAAreceptors (GABAARs) is regulated. We examined this issue in neurons of the supraoptic nucleus (SON) of the rat and found that, during parturition, the GABAARs become insensitive to the neurosteroid allopregnanolone attributable to a shift in the balance between the activities of endogenous Ser/Thr phosphatase and PKC. In particular, a constitutive endogenous tone of oxytocin within the SON after parturition suppressed neurosteroid sensitivity of GABAARs via activation of PKC. Vice versa before parturition, during late pregnancy, application of exogenous oxytocin brings the GABAARs from a neurosteroid-sensitive mode toward a …