The U.S. Department of Energy's Office of Scientific and Technical Information

J. Neurochem. (2010) 112, 1327–1337. Abstract Chronic nicotine self-administration augments the thalamo-pituitary-adrenal (HPA) responses to stress. Altered neuropeptide expression within cortico...

Experiments in our laboratory have shown that central noradrenergic (NA) activation plays a major role in stress-induced reinstatement of drug seeking in rats. In the present experiments, we investigated the effects of blockade of β-NA adrenoceptors in the bed nucleus of the stria terminalis (BNST) and in the region of the central nucleus of the amygdala (CeA) on footshock- and cocaine-induced reinstatement. Rats were trained to self-administer cocaine (0.5 mg/kg, i.v.) for 9 d and, after a 5–7 d drug-free period, were given extinction sessions followed by a test for footshock stress-induced (15 min of intermittent footshock, 0.8 mA) or cocaine-induced (20 mg/kg, i.p.) reinstatement. Before the test, different groups of rats were given bilateral infusions of one of four doses of a mixture of the β1- and β2-receptor antagonists betaxolol and ICI-118,551 (vehicle, 0.25, 0.5, and 1 nmol of each compound in 0.5 μl) into either the BNST or CeA. We observed a dose-dependent reduction of stress-induced reinstatement after infusions into the BNST and a complete blockade of stress-induced reinstatement after infusions into the CeA at all doses tested. The same treatments did not block cocaine-induced reinstatement when given at either site. These data suggest that stress-induced NA activation in the BNST and in the region of the CeA is critical to relapse to drug seeking induced by stress but not to relapse induced by priming injections of cocaine, and we hypothesize that NA activity leads to activation of corticotropin-releasing factor neurons in these regions.

Pressure switch and thermostat with two control outputs and two stages, operating in pressurization, depressurization, refrigeration, heating, or alarm mod...

Experiments in our laboratory have shown that central noradrenergic (NA) activation plays a major role in stress-induced reinstatement of drug seeking in rats. In the present experiments, we investigated the effects of blockade of β-NA adrenoceptors in the bed nucleus of the stria terminalis (BNST) and in the region of the central nucleus of the amygdala (CeA) on footshock- and cocaine-induced reinstatement. Rats were trained to self-administer cocaine (0.5 mg/kg, i.v.) for 9 d and, after a 5–7 d drug-free period, were given extinction sessions followed by a test for footshock stress-induced (15 min of intermittent footshock, 0.8 mA) or cocaine-induced (20 mg/kg, i.p.) reinstatement. Before the test, different groups of rats were given bilateral infusions of one of four doses of a mixture of the β1- and β2-receptor antagonists betaxolol and ICI-118,551 (vehicle, 0.25, 0.5, and 1 nmol of each compound in 0.5 μl) into either the BNST or CeA. We observed a dose-dependent reduction of stress-induced reinstatement after infusions into the BNST and a complete blockade of stress-induced reinstatement after infusions into the CeA at all doses tested. The same treatments did not block cocaine-induced reinstatement when given at either site. These data suggest that stress-induced NA activation in the BNST and in the region of the CeA is critical to relapse to drug seeking induced by stress but not to relapse induced by priming injections of cocaine, and we hypothesize that NA activity leads to activation of corticotropin-releasing factor neurons in these regions.

A current disturbing trend in stem cell biology is the abandonment of rigorous definitions of stem and progenitor cells in favor of more ambiguous, all-encompassing concepts. However, recent studies suggest that there are consistent, functional differences in the biology of these two cell types. Admittedly, it can be difficult to harmonize the in vivo and in vitro functional differences between stem and progenitor cells. Nonetheless, these distinctions between cell types should be emphasized rather than ignored, as they can be used to test specific hypotheses in neural stem cell biology.

The U.S. Department of Energy's Office of Scientific and Technical Information

Neuropsychopharmacology -

Cobalt-60 irradiators and soft X-ray machines are frequently used for research purposes, but the dosimetry is not always performed using the recommended protocols. This may lead to confusing and untrustworthy results within the conducted research. Postal dosimetry systems have already been approved …

To rigorously test the in vivo cell fate specificity of bone marrow (BM) hematopoietic stem cells (HSCs), we generated chimeric animals by transplantation of a single green fluorescent protein (GFP)-marked HSC into lethally irradiated nontransgenic recipients. Single HSCs robustly reconstituted peri …

Scientific Reports - 3D Dental Subsurface Imaging Using Enhanced Truncated Correlation-Photothermal...

Abstract. Although α2-adrenoceptor agonists are widely used for analgesia, anxiolysis, sedation, sympatholysis and as anaesthetic-adjuncts for many years, their

Abstract. Although α2-adrenoceptor agonists are widely used for analgesia, anxiolysis, sedation, sympatholysis and as anaesthetic-adjuncts for many years, their

Although transcriptomic profiling of kidney tissues or isolated glomeruli has provided insights into broad changes in the pathogenesis of diabetic kidney disease, the presence of multiple cell types in kidney samples limits what can be discerned about changes in specific types of cells. To better elucidate the mechanisms of early diabetic kidney injury, the authors used single-cell RNA sequencing technology to perform a gene expression analysis of individual kidney glomerular cells of a diabetic mouse model. A comparison of gene expression in normal versus diabetic mouse kidney cells at a single-cell level showed dynamic changes in the pattern of expressed genes. This approach may help identify important factors underlying the pathophysiology of diabetic kidney disease progression and point to potential new therapeutic approaches. Background Recent single-cell RNA sequencing (scRNA-seq) analyses have offered much insight into cell-specific gene expression profiles in normal kidneys. However, in diseased kidneys, understanding of changes in specific cells, particularly glomerular cells, remains limited. Methods To elucidate the glomerular cell–specific gene expression changes in diabetic kidney disease, we performed scRNA-seq analysis of isolated glomerular cells from streptozotocin-induced diabetic endothelial nitric oxide synthase (eNOS)–deficient (eNOS−/−) mice and control eNOS−/− mice. Results We identified five distinct cell populations, including glomerular endothelial cells, mesangial cells, podocytes, immune cells, and tubular cells. Using scRNA-seq analysis, we confirmed the expression of glomerular cell–specific markers and also identified several new potential markers of glomerular cells. The number of immune cells was significantly higher in diabetic glomeruli compared with control glomeruli, and further cluster analysis showed that these immune cells were predominantly macrophages. Analysis of differential gene expression in endothelial and mesangial cells of diabetic and control mice showed dynamic changes in the pattern of expressed genes, many of which are known to be involved in diabetic kidney disease. Moreover, gene expression analysis showed variable responses of individual cells to diabetic injury. Conclusions Our findings demonstrate the ability of scRNA-seq analysis in isolated glomerular cells from diabetic and control mice to reveal dynamic changes in gene expression in diabetic kidneys, with variable responses of individual cells. Such changes, which might not be apparent in bulk transcriptomic analysis of glomerular cells, may help identify important pathophysiologic factors contributing to the progression of diabetic kidney disease.

Alpha Receptor Agonist Toxicity PubMed published article

Alpha Receptor Agonist Toxicity PubMed published article

Although transcriptomic profiling of kidney tissues or isolated glomeruli has provided insights into broad changes in the pathogenesis of diabetic kidney disease, the presence of multiple cell types in kidney samples limits what can be discerned about changes in specific types of cells. To better elucidate the mechanisms of early diabetic kidney injury, the authors used single-cell RNA sequencing technology to perform a gene expression analysis of individual kidney glomerular cells of a diabetic mouse model. A comparison of gene expression in normal versus diabetic mouse kidney cells at a single-cell level showed dynamic changes in the pattern of expressed genes. This approach may help identify important factors underlying the pathophysiology of diabetic kidney disease progression and point to potential new therapeutic approaches. Background Recent single-cell RNA sequencing (scRNA-seq) analyses have offered much insight into cell-specific gene expression profiles in normal kidneys. However, in diseased kidneys, understanding of changes in specific cells, particularly glomerular cells, remains limited. Methods To elucidate the glomerular cell–specific gene expression changes in diabetic kidney disease, we performed scRNA-seq analysis of isolated glomerular cells from streptozotocin-induced diabetic endothelial nitric oxide synthase (eNOS)–deficient (eNOS−/−) mice and control eNOS−/− mice. Results We identified five distinct cell populations, including glomerular endothelial cells, mesangial cells, podocytes, immune cells, and tubular cells. Using scRNA-seq analysis, we confirmed the expression of glomerular cell–specific markers and also identified several new potential markers of glomerular cells. The number of immune cells was significantly higher in diabetic glomeruli compared with control glomeruli, and further cluster analysis showed that these immune cells were predominantly macrophages. Analysis of differential gene expression in endothelial and mesangial cells of diabetic and control mice showed dynamic changes in the pattern of expressed genes, many of which are known to be involved in diabetic kidney disease. Moreover, gene expression analysis showed variable responses of individual cells to diabetic injury. Conclusions Our findings demonstrate the ability of scRNA-seq analysis in isolated glomerular cells from diabetic and control mice to reveal dynamic changes in gene expression in diabetic kidneys, with variable responses of individual cells. Such changes, which might not be apparent in bulk transcriptomic analysis of glomerular cells, may help identify important pathophysiologic factors contributing to the progression of diabetic kidney disease.

pharmacology of alpha-agonist drugs

pharmacology of alpha-agonist drugs

A majority of people in the United States use complementary and alternative therapies, and this use is increasing. With the increasing interest, providers must evaluate potential risks and benefits of these therapies. This article describes challenges of a feasibility study of acupuncture as a poten …