Search results for " Sprague-Dawley"
showing 10 items of 639 documents
Ca2+ signalling plays a role in celastrol‐mediated suppression of synovial fibroblasts of rheumatoid arthritis patients and experimental arthritis in…
2019
Background and purpose Celastrol exhibits anti-arthritic effects in rheumatoid arthritis (RA), but the role of celastrol-mediated Ca2+ mobilization in treatment of RA remains undefined. Here, we describe a regulatory role for celastrol-induced Ca2+ signalling in synovial fibroblasts of RA patients and adjuvant-induced arthritis (AIA) in rats. Experimental approach We used computational docking, Ca2+ dynamics and functional assays to study the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase pump (SERCA). In rheumatoid arthritis synovial fibroblasts (RASFs)/rheumatoid arthritis fibroblast-like synoviocytes (RAFLS), mechanisms of Ca2+ -mediated autophagy were analysed by histological, immunohis…
Central functional response to the novel peptide cannabinoid, hemopressin.
2013
Hemopressin is the first peptide ligand to be described for the CB₁ cannabinoid receptor. Hemopressin acts as an inverse agonist in vivo and can cross the blood-brain barrier to both inhibit appetite and induce antinociception. Despite being highly effective, synthetic CB₁ inverse agonists are limited therapeutically due to unwanted, over dampening of central reward pathways. However, hemopressin appears to have its effect on appetite by affecting satiety rather than reward, suggesting an alternative mode of action which might avoid adverse side effects. Here, to resolve the neuronal circuitry mediating hemopressin's actions, we have combined blood-oxygen-level-dependent, pharmacological-ch…
Assessment of the cytotoxic potential of an aqueous-ethanolic extract from Thalassia testudinum angiosperm marine grown in the Caribbean Sea
2018
Abstract Objectives Reported antioxidant, anti-inflammatory and neuroprotective properties for one aqueous-ethanolic extract from Thalassia testudinum which grows in the Caribbean Sea compelled us to explore about extract cytotoxic effects. Methods Cell viability was assayed on tumour (HepG2, PC12, Caco-2 and 4T1) and non-tumour (VERO, 3T3, CHO, MCDK and BHK2) cell lines. The extract effects upon primary cultures of rat and human hepatocytes and human lymphocytes were assayed. Key findings The extract exhibited cytotoxicity against cancer cells compared to normal cells, and the IC50 values were 102 μg/ml for HepG2, 135 μg/ml for PC12, 165 μg/ml for Caco-2 and 129 μg/ml for 4T1 cells after 4…
Reduced oxytocin receptor gene expression and binding sites in different brain regions in schizophrenia: A post-mortem study
2016
Schizophrenia is a severe neuropsychiatric disorder with impairments in social cognition. Several brain regions have been implicated in social cognition, including the nucleus caudatus, prefrontal and temporal cortex, and cerebellum. Oxytocin is a critical modulator of social cognition and the formation and maintenance of social relationships and was shown to improve symptoms and social cognition in schizophrenia patients. However, it is unknown whether the oxytocin receptor is altered in the brain. Therefore, we used qRT-PCR and Ornithine Vasotocin Analog ([125I]OVTA)-based receptor autoradiography to investigate oxytocin receptor expression at both the mRNA and protein level in the left p…
Inward currents in primary nociceptive neurons of the rat and pain sensations in humans elicited by infrared diode laser pulses
2002
Radiant heat is often used to study nociception in vivo. We now used infrared radiation generated by a diode laser stimulator (wavelength 980 nm) to investigate transduction mechanisms for noxious heat stimuli in acutely dissociated dorsal root ganglion (DRG) neurons of rats in vitro. The laser stimulator offered the unique opportunity to test whether the same stimuli also elicit pain sensations in humans. A specific heat-induced current (I(heat)) was elicited in six of 13 small DRG neurons (diameteror =30 microm) tested in the whole-cell configuration of the patch-clamp mode. Current responses in the seven heat-insensitive neurons were within the range explainable by the temperature depend…
Spinal Endocannabinoids and CB 1 Receptors Mediate C-Fiber–Induced Heterosynaptic Pain Sensitization
2009
Plastic Pain Perception Drugs and endocannabinoids acting on cannabinoid (CB) receptors have potential in the treatment of certain types of pain. In the spinal cord they are believed to suppress nociception, the perception of pain and noxious stimuli. Pernia-Andrade et al. (p. 760 ) now find that endocannabinoids, which are released in spinal cord by noxious stimulation, may promote rather than inhibit nociception by acting on CB1 receptors. Endocannabinoids not only depress transmission at excitatory synapses in the spinal cord, but also block the release of inhibitory neurotransmitters, thereby facilitating nociception.
Menopause and ovariectomy cause a low grade of systemic inflammation that may be prevented by chronic treatment with low doses of estrogen or losarta…
2009
Abstract The incidence of cardiovascular diseases in premenopausal women is lower than in men or postmenopausal women. This study reports the discovery of a low grade of systemic inflammation, including monocyte adhesion to arterial endothelium, elicited by menopause or estrogen depletion. Chronic treatment with low dose of 17-β-estradiol or inhibition of the renin-angiotensin system reduced this inflammation. Using an in vitro flow chamber system with human arterial and venous endothelial cells, we found that leukocytes from healthy postmenopausal women were more adhesive to the arterial endothelium than those from premenopausal women regardless of the stimulus used on endothelial cells. I…
Pharmacological heterogeneity of γ-aminobutyric acid receptors during development suggests distinct classes of rat cerebellar granule cells in situ
2001
The gamma-aminobutyric acid receptor (GABA(A)R) represents a ligand-gated Cl(-)-channel assembling as heteropentamere from 19 known subunits. Cerebellar granule cells contain a unique subset, namely the alpha1-, alpha6-, beta2-, gamma2- and delta-subunits. We studied their GABAergic pharmacology in situ using whole-cell patch-clamp recordings in brain slices and a modified Y-tube application system. The distribution of the EC50s for GABA in young (P8-P14) and medium aged animals (P15-P28) could be fitted with the sum of two Gaussian distributions with means of 60 and 185 microM and 27 and 214 microM, respectively. In older animals (P29-P48) the observed homogeneous range of sensitivities fi…
Impaired calcium homeostasis in aged hippocampal neurons
2009
Abstract Development of neurodegenerative diseases such as Alzheimer's and Parkinson's disease is strongly age-associated. The impairment of calcium homeostasis is considered to be a key pathological event leading to neuronal dysfunction and cell death. However, the exact impact of aging on calcium homeostasis in neurons remains largely unknown. In the present work we have investigated intracellular calcium levels in cultured primary hippocampal neurons from young (2 months) and aged (24 months) rat brains. Upon stimulation with glutamate or hydrogen peroxide aged neurons in comparison to young neurons demonstrated an increased vulnerability to these disease-related toxins. Measurement of c…
Neuronal nicotinic receptors in synaptic functions in humans and rats: physiological and clinical relevance.
2000
The present report describes the participation of nicotinic receptors (nAChRs) in controlling the excitability of local neuronal circuitries in the rat hippocampus and in the human cerebral cortex. The patch-clamp technique was used to record responses triggered by the non-selective agonist ACh and the alpha7-nAChR-selective agonist choline in interneurons of human cerebral cortical and rat hippocampal slices. Evidence is provided that functional alpha7- and alpha4beta2-like nAChRs are present on somatodendritic and/or preterminal/terminal regions of interneurons in the CA1 field of the rat hippocampus and in the human cerebral cortex and that activation of the different nAChR subtypes pres…