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showing 10 items of 31271 documents
Atrial fibrillation and cognitive disorders: An overview on possible correlation
2020
Atrial Fibrillation is the most common cardiac arrhythmia affecting people of all ages, principally the elderly. Cognitive decline and dementia are also prevalent diseases in elderly. The scientific community always showed interest in the possible association between these two pathological entities, both implicating social and economic burden. This has been confirmed by several longitudinal population-based studies. Some studies also revealed that the association between atrial fibrillation and dementia may be not related to history of stroke. Therefore, other pathophysiological mechanisms are likely implicated, so far unclear or undefined. The aim of the present review is to analyse the po…
The Early Indicators of Functional Decrease in Mild Cognitive Impairment
2016
OBJECTIVES: Motor deficiency is associated with cognitive frailty in patients with Mild Cognitive Impairments (MCI). In this study we aimed to test the integrity of the muscle synergy involved in an arm-pointing movement in MCI patients, non-impaired functionally. Thus, we were able to test the hypothesis that early motor indicators exist in this population at a preclinical level. METHODS: The electromyographic signals were collected for 11 muscles in 3 groups: Young Adults (YA), Aged Adults (AA), and MCI patients. The AA and MCI groups presented the same functional status. Each subject performed twenty arm-pointing movements from a standing position. RESULTS: The main differences were (1) …
Sodium functions as a negative allosteric modulator of the oxytocin receptor
2017
Abstract The oxytocin receptor, a class A G protein coupled receptor (GPCR), is essentially involved in the physiology of reproduction. Two parameters are crucially important to support high-affinity agonist binding of the receptor: Mg2+ and cholesterol, both acting as positive modulators. Using displacement assays with a high-affinity fluorescent antagonist (OTAN-A647), we now show that sodium functions as a negative allosteric modulator of the oxytocin receptor. In membranes from HEK293 cells stably expressing the oxytocin receptor, oxytocin binding occurred with about 15-fold lower affinity when sodium chloride was increased from 0 to 300 mM, whereas antagonist binding remained largely u…
2019
The P-STS human ileal neuroendocrine tumor cells, as a model for gut enterochromaffin cells, are strongly and synergistically activated by histamine plus acetylcholine (ACh), presumably via histamine 4 receptors, and weakly activated by histamine alone. Sensing these signals, enterochromaffin cells could participate in intestinal intolerance or allergic reactions to food constituents associated with elevated histamine levels. In this study we aimed to analyze the underlying molecular mechanisms. Inhibition by mepyramine and mibefradil indicated that histamine alone caused a rise in intracellular calcium concentration ([Ca2+]i) via histamine 1 receptors involving T-type voltage-gated calciu…
The role of (E)-6-chloro-3-(3-methyl-1-phenyl-1H-pyrazol-5-yl)-2-styrylquinazolin-4(3H)-one in the modulation of cannabinoidergic system. A pilot stu…
2018
Abstract Background Compounds acting on endocannabinoid system regulate different neuronal processes through the cannabinoid receptors activation. The main aim of this study was determining whether the 2-styrylquinazolin-4(3H)-one 5, a structural analogue of rimonabant, was able to counteract the behavioural signs of the activation of the endocannabinoidergic system induced by CP 55.940. Methods Behavioural assessment was carried out using the tetrad task and the novel object recognition test. The endocannabinoidergic system activation was possible by the administration of CP 55.940 and 30 min after rats were tested in the tetrad task for the evaluation of the antinociceptive-, cataleptic-,…
Muscarinic type-1 receptors contribute to I-K,I-ACh in human atrial cardiomyocytes and are upregulated in patients with chronic atrial fibrillation
2018
Background: Basal and acetylcholine-gated inward-rectifier K+-currents (I-K1 and I-K,I-ACh, respectively) are altered in atrial fibrillation (AF). G(i)-protein-coupled muscarinic (M) receptors type-2 are considered the predominant receptors activating I-K,I-ACh. Although a role for G(q)-coupled non-M-2-receptor subtypes has been suggested, the precise regulation of I-K,I-ACh by multiple M-receptor subtypes in the human atrium is unknown. Here, we investigated M-1-receptor-mediated I-K,I-ACh regulation and its remodeling in chronic AF (cAF). Methods and results: M-1-receptor mRNA and protein abundance were increased in atrial cardiomyocyte fractions and atrial homogenates from cAF patients, …
Desensitization of cAMP Accumulation via Human β3-Adrenoceptors Expressed in Human Embryonic Kidney Cells by Full, Partial, and Biased Agonists
2019
β3-Adrenoceptors couple not only to cAMP formation but, at least in some cell types, also to alternative signaling pathways such as phosphorylation of extracellular signal-regulated kinase (ERK). β3-Adrenoceptor agonists are used in long-term symptomatic treatment of the overactive bladder syndrome; it is only poorly understood which signaling pathway mediates the clinical response and whether it undergoes agonist-induced desensitization. Therefore, we used human embryonic kidney cells stably transfected with human β3-adrenoceptors to compare coupling of ligands with various degrees of efficacy, including biased agonists, to cAMP formation and ERK phosphorylation, particularly regarding des…
Effects of Chronic Dopamine D2R Agonist Treatment and Polysialic Acid Depletion on Dendritic Spine Density and Excitatory Neurotransmission in the mP…
2016
Dopamine D2 receptors (D2R) in the medial prefrontal cortex (mPFC) are key players in the etiology and therapeutics of schizophrenia. The overactivation of these receptors contributes to mPFC dysfunction. Chronic treatment with D2R agonists modifies the expression of molecules implicated in neuronal structural plasticity, synaptic function, and inhibitory neurotransmission, which are also altered in schizophrenia. These changes are dependent on the expression of the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), a plasticity-related molecule, but nothing is known about the effects of D2R and PSA-NCAM on excitatory neurotransmission and the structure of mPFC pyramidal n…
Heat shock protein (Hsp) regulation by muscarinic acetylcholine receptor (mAChR) activation in the rat hippocampus.
2018
The cholinergic system plays a crucial role in modulating in the central nervous system physiological responses such as neurogenesis, neuronal differentiation, synaptic plasticity, and neuroprotection. In a recent study, we showed that Oxotremorine-M, a non-selective muscarinic acetylcholine receptor agonist, is able to transactivate the fibroblast growth factor receptor and to produce a significant increase in the hippocampal primary neurite outgrowth. In the present study we aimed to explore in the rat hippocampus the possible effect of acute or chronic treatment with Oxotremorine-M on some heat shock proteins (Hsp60, Hsp70, Hsp90) and on activation of related transcription factor heat sh…
Do β3-adrenoceptor agonists cause urinary bladder smooth muscle relaxation by inhibiting acetylcholine release?
2017
The mechanisms leading to improvement of overactive bladder syndrome upon treatment with a β3-adrenoceptor agonist remain controversial. New research points to a role of inhibition of neuronal acetylcholine release. Whether this occurs by a direct effect on prejunctional β3-adrenoceptors or indirectly by formation of adenosine and activation of A1 adenosine receptors is being discussed.