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Consequences of Acetylcholine imbalance

X A Perez, T Bordia, M Quik
Cholinergic signaling plays a key role in regulating striatal function. The principal source of acetylcholine in the striatum is the cholinergic interneurons which, although low in number, densely arborize to modulate striatal neurotransmission. This modulation occurs via strategically positioned nicotinic and muscarinic acetylcholine receptors that influence striatal dopamine, GABA and other neurotransmitter release. Cholinergic interneurons integrate multiple striatal synaptic inputs and outputs to regulate motor activity under normal physiological conditions...
August 2018: Journal of Neural Transmission
Man Xu, Xueyuan Bi, Xi He, Xiaojiang Yu, Ming Zhao, Weijin Zang
The mitochondrial unfolded protein response (UPR(mt)) is involved in numerous diseases that have the common feature of mitochondrial dysfunction. However, its pathophysiological relevance in the context of hypoxia/reoxygenation (H/R) in endothelial cells remains elusive. Previous studies have demonstrated that acetylcholine (ACh) protects against cardiomyocyte injury by suppressing generation of mitochondrial reactive oxygen species (mtROS). This study aimed to explore the role of UPR(mt) in endothelial cells during H/R and to clarify the beneficial effects of ACh...
May 18, 2016: Cell Cycle
Ana María Gamez-Mendez, Hilda Vargas-Robles, Amelia Ríos, Bruno Escalante
Obesity is involved in several cardiovascular diseases including coronary artery disease and endothelial dysfunction. Endothelial Endothelium vasodilator and vasoconstrictor agonists play a key role in regulation of vascular tone. In this study, we evaluated coronary vascular response in an 8 weeks diet-induced obese C57BL/6 mice model. Coronary perfusion pressure in response to acetylcholine in isolated hearts from obese mice showed increased vasoconstriction and reduced vasodilation responses compared with control mice...
2015: PloS One
Marc Deffains, Hagai Bergman
Basal ganglia disorders such as Parkinson's disease, dystonia, and Huntington's disease are characterized by a dysregulation of the basal ganglia neuromodulators (dopamine, acetylcholine, and others), which impacts cortico-striatal transmission. Basal ganglia disorders are often associated with an imbalance between the midbrain dopaminergic and striatal cholinergic systems. In contrast to the extensive research and literature on the consequences of a malfunction of midbrain dopaminergic signaling on the plasticity of the cortico-striatal synapse, very little is known about the role of striatal cholinergic interneurons in normal and pathological control of cortico-striatal transmission...
July 2015: Movement Disorders: Official Journal of the Movement Disorder Society
Shoin Tei, Hiroshige T Ishii, Hiroaki Mitsuhashi, Shoichi Ishiura
CHRNA1 encodes the α subunit of nicotinic acetylcholine receptors (nAChRs) and is expressed at the neuromuscular junction. Moreover, it is one of the causative genes of Congenital Myasthenic Syndromes (CMS). CHRNA1 undergoes alternative splicing to produce two splice variants: P3A(-), without exon P3A, and P3A(+), with the exon P3A. Only P3A(-) forms functional nAChR. Aberrant alternative splicing caused by intronic or exonic point mutations in patients leads to an extraordinary increase in P3A(+) and a concomitant decrease in P3A(-)...
June 5, 2015: Biochemical and Biophysical Research Communications
Jill R Crittenden, Carolyn J Lacey, Tyrone Lee, Hilary A Bowden, Ann M Graybiel
In drug users, drug-related cues alone can induce dopamine release in the dorsal striatum. Instructive cues activate inputs to the striatum from both dopaminergic and cholinergic neurons, which are thought to work together to support motor learning and motivated behaviors. Imbalances in these neuromodulatory influences can impair normal action selection and might thus contribute to pathologically repetitive and compulsive behaviors such as drug addiction. Dopamine and acetylcholine can have either antagonistic or synergistic effects on behavior, depending on the state of the animal and the receptor signaling systems at play...
2014: Frontiers in Neural Circuits
Reinhard Schliebs, Thomas Arendt
The basal forebrain cholinergic complex comprising medial septum, horizontal and vertical diagonal band of Broca, and nucleus basalis of Meynert provides the mayor cholinergic projections to the cerebral cortex and hippocampus. The cholinergic neurons of this complex have been assumed to undergo moderate degenerative changes during aging, resulting in cholinergic hypofunction that has been related to the progressing memory deficits with aging. However, the previous view of significant cholinergic cell loss during aging has been challenged...
August 10, 2011: Behavioural Brain Research
A Ciobică, L Hriţcu, V Artenie, Manuela Pădurariu
Reactive oxygen species (ROS) are produced within the body during oxygen metabolism and living organisms have developed several defense mechanisms to protect themselves from oxidative stress. Under normal conditions, ROS and antioxidant systems are in balance. Oxidative stress is caused by the imbalance between production of pro-oxidants and the antioxidant defenses. The defense mechanisms include antioxidant enzymes like superoxide dismutase (SOD) or glutathione peroxidase (GPX) and several no enzymatic free radical scavengers...
July 2009: Revista Medico-chirurgicală̆ a Societă̆ţ̜ii de Medici ş̧i Naturaliş̧ti Din Iaş̧i
Aline Lara, Denis D Damasceno, Rita Pires, Robert Gros, Enéas R Gomes, Mariana Gavioli, Ricardo F Lima, Diogo Guimarães, Patricia Lima, Carlos Roberto Bueno, Anilton Vasconcelos, Danilo Roman-Campos, Cristiane A S Menezes, Raquel A Sirvente, Vera M Salemi, Charles Mady, Marc G Caron, Anderson J Ferreira, Patricia C Brum, Rodrigo R Resende, Jader S Cruz, Marcus Vinicius Gomez, Vania F Prado, Alvair P de Almeida, Marco A M Prado, Silvia Guatimosim
Overwhelming evidence supports the importance of the sympathetic nervous system in heart failure. In contrast, much less is known about the role of failing cholinergic neurotransmission in cardiac disease. By using a unique genetically modified mouse line with reduced expression of the vesicular acetylcholine transporter (VAChT) and consequently decreased release of acetylcholine, we investigated the consequences of altered cholinergic tone for cardiac function. M-mode echocardiography, hemodynamic experiments, analysis of isolated perfused hearts, and measurements of cardiomyocyte contraction indicated that VAChT mutant mice have decreased left ventricle function associated with altered calcium handling...
April 2010: Molecular and Cellular Biology
A Púzserová, J Kopincová, I Bernátová
Vascular system is a large complex of tubes with different diameters which are able to perceive changes of endogenous milieu, to integrate and modulate signals of intercellular communication and to respond and adapt by a local production of different kinds of mediators affecting vascular structure and function. For a long time, it has been assumed that the main determinant of vasomotor function was the nervous system and the monolayer of endothelial cells was only a physical barrier between the vessel wall and blood...
2008: Ceskoslovenská Fysiologie
L Di Cesare Mannelli, A Bartolini, C Ghelardini
Traumatic, infectious, metabolic, and chemical noxa to the nervous system are the etiology of a crippling disease generally termed neuropathy. Motor disorders, altered sensibility, and pain are the pathognomonic traits. Cellular alterations induced by this chronic pathology include mitochondrial dysfunctions that lead to the activation of the apoptotic cascade. Energy imbalance can compromise the maintenance of mitochondrial membrane potential, furthering the release of cytochrome C and the subsequent cleavage and activation of caspases...
June 2009: Journal of Neuroscience Research
Milagros I Figueroa-Ramos, Carmen Mabel Arroyo-Novoa, Kathryn A Lee, Geraldine Padilla, Kathleen A Puntillo
Sleep deprivation and delirium are conditions commonly encountered in intensive care unit patients. Sleep in these patients is characterized by sleep fragmentation, an increase in light sleep, and a decrease of both slow wave sleep and rapid eye movement sleep. The most common types of delirium in this population are hypoactive and mixed-type. Knowledge about the mechanisms of sleep and delirium has evolved over time, but these phenomena are not yet well understood. What is known, however, is that different areas in the brainstem transmit information to the thalamus and cortex necessary for sleep-wake regulation...
May 2009: Intensive Care Medicine
María-Salud García-Ayllón, Omar Cauli, María-Ximena Silveyra, Regina Rodrigo, Asunción Candela, Antonio Compañ, Rodrigo Jover, Miguel Pérez-Mateo, Salvador Martínez, Vicente Felipo, Javier Sáez-Valero
The cholinergic system is involved in specific behavioural responses and cognitive processes. Here, we examined potential alterations in the brain levels of key cholinergic enzymes in cirrhotic patients and animal models with liver failure. An increase (~30%) in the activity of the acetylcholine-hydrolyzing enzyme, acetylcholinesterase (AChE) is observed in the brain cortex from patients deceased from hepatic coma, while the activity of the acetylcholine-synthesizing enzyme, choline acetyltransferase, remains unaffected...
November 2008: Brain
Zheng-Xuan Shen
Recent evidence strongly demonstrates that acetylcholine (ACh) is not only involved in the function of the central and peripheral nervous systems, including the parasympathetic and somatic systems, but also acts as a ubiquitous cell signaling molecule or cytotransmitter, and as a hormone with paracrine, juxtacrine and autocrine properties. This active molecule exerts versatile and potent functions primarily through its specific nicotinic and muscarinic receptors (nAChRs and mAChRs, respectively). These functions modulate numerous biomechanisms, including cell growth, survival, proliferation and differentiation, cell-cell contact, cell cycle, locomotion, electrical activity, immune function, apoptosis, organization of the cytoskeleton, trophic functions, secretion, adhesion, resorption, and stress-response-regulation...
2008: Medical Hypotheses
Katalin Sas, Hermina Robotka, József Toldi, László Vécsei
The mitochondria have several important functions in the cell. A mitochondrial dysfunction causes an abatement in ATP production, oxidative damage and the induction of apoptosis, all of which are involved in the pathogenesis of numerous disorders. This review focuses on mitochondrial dysfunctions and discusses their consequences and potential roles in the pathomechanism of neurodegenerative disorders. Other pathogenetic factors are also briefly surveyed. The second part of the review deals with the kynurenine metabolic pathway, its alterations and their potential association with cellular energy impairment in certain neurodegenerative diseases...
June 15, 2007: Journal of the Neurological Sciences
N Müller, M J Schwarz
This manuscript deals with whether immune-mediated mechanisms of inflammation contribute to the pathogenesis of schizophrenia. A model is presented which integrates psychoneuroimmunologic findings and actual results from pharmacological, neurochemical, and genetic studies in schizophrenia. A pivotal role in the neurobiology of schizophrenia is played by dopaminergic neurotransmission, which is modulated by influences of the glutamatergic system. The decreased function of the glutamate system described in schizophrenia seems primarily mediated by N-methyl-D-aspartate (NMDA) receptor antagonism...
March 2007: Der Nervenarzt
Ji-Shi Wang, Harpreet Singh, Frank Zhang, Tsuneo Ishizuka, Huan Deng, Rowena Kemp, Michael S Wolin, Thomas H Hintze, Nader G Abraham, Alberto Nasjletti, Michal Laniado-Schwartzman
Vascular cytochrome P450 (CYP) 4A enzymes catalyze the synthesis of 20-hydroxyeicosatetraenoic acid (20-HETE), an eicosanoid which participates in the regulation of vascular tone by sensitizing the smooth muscle cells to constrictor and myogenic stimuli. This study was undertaken to investigate the consequences of CYP4A overexpression on blood pressure and endothelial function in rats treated with adenoviral vectors carrying the CYP4A2 construct. Intravenous injection of Adv-CYP4A2 increased blood pressure (from 114+/-1 to 133+/-1 mm Hg, P<0...
April 14, 2006: Circulation Research
M Garcia-Alloza, F J Gil-Bea, M Diez-Ariza, C P L-H Chen, P T Francis, B Lasheras, M J Ramirez
Neuropsychiatric symptoms seen in Alzheimer's disease (AD) are not simply a consequence of neurodegeneration, but probably result from differential neurotransmitter alterations, which some patients are more at risk of than others. Therefore, the hypothesis of this study is that an imbalance between the cholinergic and serotonergic systems is related to cognitive symptoms and psychological syndromes of dementia (BPSD) in patients with AD. Cholinergic and serotonergic functions were assessed in post-mortem frontal and temporal cortex from 22 AD patients who had been prospectively assessed with the Mini-Mental State examination (MMSE) for cognitive impairment and with the Present Behavioral Examination (PBE) for BPSD including aggressive behavior, overactivity, depression and psychosis...
2005: Neuropsychologia
J Tam, N Danilovich, K Nilsson, M R Sairam, D Maysinger
The follitropin receptor knockout (FORKO) mouse undergoes ovarian failure, thereby providing an animal model to investigate the consequences of the depletion of circulating estrogen in females. The estrogen deficiency causes marked defects in the female reproductive system, obesity, and skeletal abnormalities. In light of estrogen's known pleiotropic effects in the nervous system, our study examined the effects of genetically induced estrogen-testosterone imbalance on this system in female FORKO mice. Circulating concentrations of 17-beta-estradiol (E2) in FORKO mice are significantly decreased (FORKO -/-: 1...
2002: Neuroscience
A Jungwirth
Erectile dysfunction is an entity associated with age but is not necessarily a consequence of aging. During erection the penis acts as a capacitor--accumulating blood under pressure. Erectile function is, therefore, dependent on the integration and regulation of functional interplay between psychologic, neurologic, endocrine and vasoactive factors. Any imbalance in the integration of these factors will result in erectile dysfunction. Trabecular smooth muscle is an important structure, which contributes to control of detumescence and erection...
2000: Wiener Medizinische Wochenschrift
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