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Cholinergic receptor

Marion T Turnbull, Elizabeth J Coulson
Alzheimer's disease (AD) is a progressive, irreversible neurodegenerative disease that destroys memory and cognitive function. Aggregates of hyperphosphorylated tau protein are a prominent feature in the brain of patients with AD, and are a major contributor to neuronal toxicity and disease progression. However, the factors that initiate the toxic cascade that results in tau hyperphosphorylation in sporadic AD are unknown. Here we investigated whether degeneration of basal forebrain cholinergic neurons (BFCNs) and/or a resultant decrease in neurotrophin signaling cause aberrant tau hyperphosphorylation...
October 20, 2016: Journal of Alzheimer's Disease: JAD
Min-Soo Kim, Ji Hye Bang, Jun Lee, Jung-Soo Han, Tae Gon Baik, Won Kyung Jeon
BACKGROUND: Ginkgo biloba extract (GBE)-a widely used nutraceutical-is reported to have diverse functions, including positive effects on memory and vasodilatory properties. Although numerous studies have assessed the neuroprotective properties of GBE in ischemia, only a few studies have investigated the neuro-pharmacological mechanisms of action of GBE in chronic cerebral hypoperfusion (CCH). PURPOSE: In the present study, we sought to determine the effects of GBE on CCH-induced neuroinflammation and cholinergic dysfunction in a rat model of bilateral common carotid artery occlusion (BCCAo)...
November 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
X M Chen, F Q Li, S Yan, X C Wu, C L Tang
OBJECTIVE: To investigate the anti-inflammation effects by activation of the cholinergic anti-inflammatory pathway and its mechanisms in non-alcoholic steatohepatitis (NASH) model mice. METHODS: 6-week-old male C57BL/6J (B6) mice were randomly divided into four groups: the first group was normal mice, injected with saline; the second group was normal mice, injected with nicotine; the third group was NASH model mice, injected with saline; the fourth group was NASH model mice, injected with nicotine...
October 18, 2016: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
Tanja Mayer, Jürgen Kopitz, Konstanze Plaschke, Johanna Weiss, Hanna M Seidling, Walter E Haefeli
OBJECTIVE: The anticholinergic activity (AA) assay is a common method to determine a patient's anticholinergic load. Several limitations, however, are expected when applying the AA assay to patients or using drug scales to estimate anticholinergic burden based on AA levels. This study aims to demonstrate common pitfalls in an experimental setting and outline their clinical consequences. METHODS: The AA was analyzed for five drugs with reported interaction with muscarinic receptors...
August 4, 2016: American Journal of Geriatric Psychiatry
Marie Gendrel, Emily G Atlas, Oliver Hobert
Neurotransmitter maps are important complements to anatomical maps and represent an invaluable resource to understand nervous system function and development. We report here a comprehensive map of neurons in the C. elegans nervous system that contain the neurotransmitter GABA, revealing twice as many GABA-positive neuron classes as previously reported. We define previously unknown glia-like cells that take up GABA, as well as 'GABA uptake neurons' which do not synthesize GABA but take it up from the extracellular environment, and we map the expression of previously uncharacterized ionotropic GABA receptors...
October 14, 2016: ELife
Joachim Behar, Ambhighainath Ganesan, Jin Zhang, Yael Yaniv
Sinoatrial nodal cells (SANCs) generate spontaneous action potentials (APs) that control the cardiac rate. The brain modulates SANC automaticity, via the autonomic nervous system, by stimulating membrane receptors that activate (adrenergic) or inactivate (cholinergic) adenylyl cyclase (AC). However, these opposing afferents are not simply additive. We showed that activation of adrenergic signaling increases AC-cAMP/PKA signaling, which mediates the increase in the SANC AP firing rate (i.e., positive chronotropic modulation)...
2016: Frontiers in Physiology
Nathalia M Pinheiro, Fernanda P R Santana, Rafael Ribeiro Almeida, Marina Guerreiro, Milton A Martins, Luciana C Caperuto, Niels O S Câmara, Lislaine A Wensing, Vânia F Prado, Iolanda F L C Tibério, Marco Antônio M Prado, Carla M Prado
Nicotinic α-7 acetylcholine receptor (nAChRα7) is a critical regulator of cholinergic anti-inflammatory actions in several diseases, including acute respiratory distress syndrome (ARDS). Given the potential importance of α7nAChR as a therapeutic target, we evaluated whether PNU-282987, an α7nAChR agonist, is effective in protecting the lung against inflammation. We performed intratracheal instillation of LPS to generate acute lung injury (ALI) in C57BL/6 mice. PNU-282987 treatment, either before or after ALI induction, reduced neutrophil recruitment and IL-1β, TNF-α, IL-6, keratinocyte chemoattractant (KC), and IL-10 cytokine levels in the bronchoalveolar lavage fluid (P < 0...
October 11, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Syeda Mehpara Farhat, Touqeer Ahmed
Alzheimer&#039;s disease, a neurodegenerative disorder, is characterized by accumulation of amyloid beta (Aβ) plaques, neurofibrillary tangles and loss of cholinergic neurons. The localization of Aβ plaques particularly in the cholinergic neuron-rich areas has led to the discovery that Aβ binds to α7 nicotinic acetylcholine receptors (nAChRs) with very high affinity. This discovery has led to extensive exploration of the possible outcomes of this binding, ranging from the subcellular signaling pathways to its effects on behavioral and cognitive functions...
October 5, 2016: Current Drug Targets
Barbara J Morley, Anna Lysakowski, Sarath Vijayakumar, Deanna Menapace, Timothy A Jones
Little is known about the function of the cholinergic efferents innervating peripheral vestibular hair cells. We measured vestibular sensory evoked potentials (VsEPs) in α9 knockout mice, α10 knockout mice, α7 knockout mice, α9/10 and α7/9 double knockouts, and wild type controls. We also studied the morphology and ultrastructure of efferent terminals on vestibular hair cells in α9, α10 and α9/10 knockouts. Both type I and type ll vestibular hair cells express the α9 and α10 subunits. The efferent boutons on vestibular cells in α9, α10 and α9/10 knockouts appeared normal, but a quantitative analysis was not performed...
October 7, 2016: Journal of Comparative Neurology
Edward Ofori, Xue Y Zhu, Jagan R Etukala, Barbara A Bricker, Seth Y Ablordeppey
Diseases of the CNS are often complex and involve multiple receptor systems and thus, the treatment options for these diseases must focus on targeting the multiple receptors implicated in the various disorders. Schizophrenia and depression are examples of such diseases and their pharmacotherapy thus depends on agents which target multiple receptors including the dopamine, serotonin and even cholinergic receptors at the same time. In our previous campaign to find multi-receptor ligands, we have identified the benzothiazole 1a as an initial lead molecule...
September 10, 2016: Bioorganic & Medicinal Chemistry
Sudarat Nimitvilai, Chang You, Devinder S Arora, Maureen A McElvain, Bertha J Vandegrift, Mark S Brodie, John J Woodward
Drugs of abuse increase the activity of dopaminergic neurons of the ventral tegmental area (VTA), and output from the VTA is critical for both natural and drug-induced reward and reinforcement. Ethanol and the abused inhalant toluene both enhance VTA neuronal firing, but the mechanisms of this effect is not fully known. In this study, we used extracellular recordings to compare the actions of toluene and ethanol on DA VTA neurons. Both ethanol and toluene increased the firing rate of DA neurons, although toluene was ~100 times more potent than ethanol...
2016: Frontiers in Neuroscience
Guanglin Kuang, Xu Wang, Christer Halldin, Agneta Nordberg, Bengt Långström, Hans Ågren, Yaoquan Tu
Potentiation of the function of the α7 nicotinic acetylcholine receptor (α7-nAChR) is believed to provide a possible way for the treatment of cholinergic system dysfunctions such as Alzheimer's disease and schizophrenia. Positive allosteric modulators (PAMs) are able to augment the peak current response of the endogenous agonist of α7-nAChR by binding to some allosteric sites. In this study, the binding profile of a potent type I PAM, NS-1738, with a chimera structure (termed α7-AChBP) constructed from the extracellular domain of α7-nAChR and an acetylcholine binding protein was investigated with molecular docking, molecular dynamics simulation, and free energy calculation methods...
October 12, 2016: Physical Chemistry Chemical Physics: PCCP
Mohamed B Abou-Donia, Briana Siracuse, Natasha Gupta, Ashly Sobel Sokol
Sarin (GB, O-isopropyl methylphosphonofluoridate) is a potent organophosphorus (OP) nerve agent that inhibits acetylcholinesterase (AChE) irreversibly. The subsequent build-up of acetylcholine (ACh) in the central nervous system (CNS) provokes seizures and, at sufficient doses, centrally-mediated respiratory arrest. Accumulation of ACh at peripheral autonomic synapses leads to peripheral signs of intoxication and overstimulation of the muscarinic and nicotinic receptors, which is described as "cholinergic crisis" (i...
October 5, 2016: Critical Reviews in Toxicology
Marlene A Wilson, Jim R Fadel
Cholinergic activation regulates cognitive function, particularly long-term memory consolidation. This Review presents an overview of the anatomical, neurochemical, and pharmacological evidence supporting the cholinergic regulation of Pavlovian contextual and cue-conditioned fear learning and extinction. Basal forebrain cholinergic neurons provide inputs to neocortical regions and subcortical limbic structures such as the hippocampus and amygdala. Pharmacological manipulations of muscarinic and nicotinic receptors support the role of cholinergic processes in the amygdala, hippocampus, and prefrontal cortex in modulating the learning and extinction of contexts or cues associated with threat...
October 5, 2016: Journal of Neuroscience Research
Wei-Chia Lee, You-Lin Tain, Kay L H Wu, Steve Leu, Julie Y H Chan
Maternal fructose exposure (MFE) programs the development of metabolic syndrome (MetS) in young adult offspring. Epidemiological data indicate that MetS may increase the risks of overactive bladder (OAB) symptoms. However, it remains unknown whether MFE programs MetS-associated bladder dysfunction in adult offspring. Using Sprague-Dawley rats, we investigated the effects of MFE during pregnancy and lactation on developmental programming of MetS-associated bladder dysfunction. In addition, next generation sequencing technology was used to identify potential transcripts involved in the programmed bladder dysfunction in adult male offspring to MFE...
October 5, 2016: Scientific Reports
David Goyer, Stefanie Kurth, Charlène Gillet, Christian Keine, Rudolf Rübsamen, Thomas Kuenzel
Sensory processing in the lower auditory pathway is generally considered to be rigid and thus less subject to modulation than central processing. However, in addition to the powerful bottom-up excitation by auditory nerve fibers, the ventral cochlear nucleus also receives efferent cholinergic innervation from both auditory and nonauditory top-down sources. We thus tested the influence of cholinergic modulation on highly precise time-coding neurons in the cochlear nucleus of the Mongolian gerbil. By combining electrophysiological recordings with pharmacological application in vitro and in vivo, we found 55-72% of spherical bushy cells (SBCs) to be depolarized by carbachol on two time scales, ranging from hundreds of milliseconds to minutes...
September 2016: ENeuro
Alexander M Herman, Joshua Ortiz-Guzman, Mikhail Kochukov, Isabella Herman, Kathleen B Quast, Jay M Patel, Burak Tepe, Jeffrey C Carlson, Kevin Ung, Jennifer Selever, Qingchun Tong, Benjamin R Arenkiel
Atypical food intake is a primary cause of obesity and other eating and metabolic disorders. Insight into the neural control of feeding has previously focused mainly on signalling mechanisms associated with the hypothalamus, the major centre in the brain that regulates body weight homeostasis. However, roles of non-canonical central nervous system signalling mechanisms in regulating feeding behaviour have been largely uncharacterized. Acetylcholine has long been proposed to influence feeding owing in part to the functional similarity between acetylcholine and nicotine, a known appetite suppressant...
October 3, 2016: Nature
Asante R Kamkwalala, Paul A Newhouse
The major components of the cholinergic receptor system of the human brain include projections from the basal forebrain nuclei, and utilize the two types of receptors that they synapse on, nicotinic and muscarinic acetylcholine receptors. With the widespread cortical and subcortical projections of the basal forebrain, activity of these two receptor systems provide modulation of neurotransmitter activity underlying normal cognitive processes, such as attention, episodic memory, and working memory. Alzheimer's disease (AD) targets and damages cholinergic neurons in the basal forebrain, and as these projections are lost, cognitive performance progressively declines...
September 30, 2016: Current Alzheimer Research
Musaddique Hussain, Hafiz Muhammad Waqas, Shahid Masood Raza, Umer Farooq, Muhammad Masood Ahmed, Abdul Majeed
ETHNOPHARMACOLOGICAL RELEVANCE: Seeds of Sisymbrium irio Linn has been used traditionally in different regions of Pakistan for the treatment of gastrointestinal, airways and vascular system ailments. To insight the pharmacological basis, in vitro study was conducted in order to validate its folkloric uses. MATERIAL AND METHODS: 70% aqueous-methanolic extract of seeds from S. irio (Si.MEs) was tested on isolated rabbit aorta, jejunum and trachea strip hanged in tissue bath having physiological solutions aerated with carbogen and their responses were measured and recorded via Power Lab...
September 29, 2016: Journal of Ethnopharmacology
Priya Revathikumar, Filip Bergqvist, Srividya Gopalakrishnan, Marina Korotkova, Per-Johan Jakobsson, Jon Lampa, Erwan Le Maître
BACKGROUND: The cholinergic anti-inflammatory pathway (CAP) primarily functions through acetylcholine (ACh)-alpha7 nicotinic acetylcholine receptor (α7nAChR) interaction on macrophages to control peripheral inflammation. Interestingly, ACh can also bind α7nAChRs on microglia resulting in neuroprotective effects. However, ACh effects on astrocytes remain elusive. Here, we investigated the effects of nicotine, an ACh receptor agonist, on the cytokine and cholinesterase production of immunocompetent human astrocytes stimulated with interleukin 1β (IL-1β) in vitro...
September 29, 2016: Journal of Neuroinflammation
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