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Cholinergic Modulation (cholinergic + modulation)
Selected AbstractsCholinergic modulation of visuospatial responding in central thalamusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2007Lori A. Newman Abstract Central thalamus has extensive connections with basal ganglia and frontal cortex that are thought to play a critical role in sensory-guided goal-directed behavior. Central thalamic activity is influenced by cholinergic projections from mesopontine nuclei. To elucidate this function we trained rats to respond to lights in a reaction time (RT) task and compared effects of muscarinic (2.4, 7.3, 22 nmol scopolamine) and nicotinic (5.4, 16, 49, 98 nmol mecamylamine) antagonists with the GABAA agonist muscimol (0.1, 0.3, 1.0 nmol) in central thalamus. We compared this with subcutaneous (systemic) effects of mecamylamine (3.2, 9.7, 29 µmol/kg) and scopolamine (0.03, 0.09, 0.26 µmol/kg). Subcutaneous scopolamine increased omissions (failure to respond within a 3-s response window) at the highest dose tested. Subcutaneous mecamylamine increased omissions at the highest dose tested while impairing RT and per cent correct at lower doses. Intrathalamic injections of muscimol and mecamylamine decreased per cent correct at doses that did not affect omissions or RT. Intrathalamic scopolamine increased omissions and RT at doses that had little effect on per cent correct. Anatomical controls indicated that the effects of mecamylamine were localized in central thalamus and those of scopolamine were not. Drug effects did not interact with attention-demanding manipulations of stimulus duration, proximity of stimulus and response locations, or stimulus array size. These results are consistent with the hypothesis that central thalamus mediates decisional processes linking sensory stimuli with actions, downstream from systems that detect sensory signals. They also provide evidence that this function is specifically influenced by nicotinic cholinergic receptors. [source] Cholinergic modulation of angiogenesis: Role of the 7 nicotinic acetylcholine receptorJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2009Jenny C.F. Wu Abstract Pathological angiogenesis contributes to tobacco-related diseases such as malignancy, atherosclerosis and age-related macular degeneration. Nicotine acts on endothelial nicotinic acetylcholine receptors (nAChRs) to activate endothelial cells and to augment pathological angiogenesis. In the current study, we studied nAChR subunits involved in these actions. We detected mRNA for all mammalian nAChR subunits except ,2, ,4, ,, and , in four different types of ECs. Using siRNA methodology, we found that the ,7 nAChR plays a dominant role in nicotine-induced cell signaling (assessed by intracellular calcium and NO imaging, and studies of protein expression and phosphorylation), as well as nicotine-activated EC functions (proliferation, survival, migration, and tube formation). The ,9 and ,7 nAChRs have opposing effects on nicotine-induced cell proliferation and survival. Our studies reveal a critical role for the ,7 nAChR in mediating the effects of nicotine on the endothelium. Other subunits play a modulatory role. These findings may have therapeutic implications for diseases characterized by pathological angiogenesis. J. Cell. Biochem. 108: 433,446, 2009. © 2009 Wiley-Liss, Inc. [source] Muscarinic receptors: do they have a role in the pathology and treatment of schizophrenia?JOURNAL OF NEUROCHEMISTRY, Issue 5 2008Elizabeth Scarr Abstract The high affinity of antipsychotic drugs for the dopamine D2 receptor focused attention onto the role of these receptors in the genesis of psychoses and the pathology of schizophrenia. However, psychotic symptoms are only one aspect of the complex symptom profile associated with schizophrenia. Therefore, research continues into other neurochemical systems and their potential roles in key features associated with schizophrenia. Modulating the cholinergic system in attempts to treat schizophrenia predates specific neurochemical hypotheses of the disorder. Cholinergic modulation has progressed from the use of coma therapy, through the use of anti-cholinergic drugs to control side-effects of older (typical) antipsychotic medications, to the development of drugs designed to specifically activate selected muscarinic receptors. This review presents data implicating a decrease in muscarinic receptors, particularly the M1 receptor, in the pathology of schizophrenia and explores the potential physiological consequences of such a change, drawing on data available from muscarinic receptor knockout mice as well as clinical and pre-clinical pharmacology. The body of evidence presented suggests that deficits in muscarinic receptors are associated with some forms of schizophrenia and that targeting these receptors could prove to be of therapeutic benefit to patients with the disorder. [source] Cholinergic modulation of synaptic physiology in deep layer entorhinal cortex of the ratJOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2001Mi Young Cheong Abstract We have recently shown that cholinergic effects on synaptic transmission and plasticity in the superficial (II/III) layers of the rat medial entorhinal cortex (EC) are similar, but not identical, to those in the hippocampus (Yun et al. [2000] Neuroscience 97:671,676). Because the superficial and deep layers of the EC preferentially convey afferent and efferent hippocampal projections, respectively, it is of interest to compare cholinergic effects between the two regions. We therefore investigated the physiological effects of cholinergic agents in the layer V of medial EC slices under experimental conditions identical to those in the previous study. Bath application of carbachol (0.5 ,M) induced transient depression of field potential responses in all cases tested (30 of 30; 18.5% ± 2.3%) and rarely induced long-lasting potentiation (only 3 of 30; 20.4% ± 3.2% in successful cases). At 5 ,M, carbachol induced transient depression only (20 of 20, 48.9% ± 2.8%), which was blocked by atropine (10 ,M). Paired-pulse facilitation was enhanced during carbachol-induced depression, suggesting presynaptic action of carbachol. Long-term potentiation (LTP) could be induced in the presence of 10 ,M atropine by theta burst stimulation, but its magnitude was significantly lower (9.1% ± 4.7%, n = 15) compared to LTP in control slices (22.4% ± 3.9%, n = 20). These results, combined with our previous findings, demonstrate remarkably similar cholinergic modulation of synaptic transmission and plasticity across the superficial and deep layers of EC. J. Neurosci. Res. 66:117,121, 2001. © 2001 Wiley-Liss, Inc. [source] Acetyl-l-carnitine in the treatment of painful antiretroviral toxic neuropathy in human immunodeficiency virus patients: an open label studyJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2006Maurizio Osio Abstract Antiretroviral toxic neuropathy causes morbidity in human immunodeficiency virus (HIV) patients under dideoxynucleoside therapy, benefits only partially from medical therapy, and often leads to drug discontinuation. Proposed pathogeneses include a disorder of mitochondrial oxidative metabolism, eventually related to a reduction of mitochondrial DNA content, and interference with nerve growth factor activity. Carnitine is a substrate of energy production reactions in mitochondria and is involved in many anabolic reactions. Acetyl carnitine treatment promotes peripheral nerve regeneration and has neuroprotective properties and a direct analgesic role related to glutamatergic and cholinergic modulation. The aim of this study was to evaluate acetyl-l-carnitine in the treatment of painful antiretroviral toxic neuropathy in HIV patients. Twenty subjects affected by painful antiretroviral toxic neuropathy were treated with oral acetyl-l-carnitine at a dose of 2,000 mg/day for a 4-week period. Efficacy was evaluated by means of the modified Short Form McGill Pain Questionnaire with each item rated on an 11-point intensity scale at weekly intervals and by electromyography at baseline and final visit. Mean pain intensity score was significantly reduced during the study, changing from 7.35 ± 1.98 (mean ± SD) at baseline to 5.80 ± 2.63 at week 4 (p = 0.0001). Electrophysiological parameters did not significantly change between baseline and week 4. In this study, acetyl-l-carnitine was effective and well tolerated in symptomatic treatment of painful neuropathy associated with antiretroviral toxicity. On the contrary, no effect was noted on neurophysiological parameters. [source] | ||||||||||