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Acetylcholine imbalance

Asami Tanimura, Yijuan Du, Jyothisri Kondapalli, David L Wokosin, D James Surmeier
The motor symptoms of Parkinson's disease (PD) are thought to stem from an imbalance in the activity of striatal direct- and indirect-pathway spiny projection neurons (SPNs). Disease-induced alterations in the activity of networks controlling SPNs could contribute to this imbalance. One of these networks is anchored by the parafascicular nucleus (PFn) of the thalamus. To determine the role of the PFn in striatal PD pathophysiology, optogenetic, chemogenetic, and electrophysiological tools were used in ex vivo slices from transgenic mice with region-specific Cre recombinase expression...
January 4, 2019: Neuron
Run-Qing Xue, Xiao-Jiang Yu, Ming Zhao, Man Xu, Qing Wu, Yan-Ling Cui, Si Yang, Dong-Ling Li, Wei-Jin Zang
Insulin resistance and autonomic imbalance are important pathological processes in metabolic syndrome-induced cardiac remodeling. Recent studies determined that disruption of mitochondrial cristae shape is associated with myocardial ischemia; however, the change in cristae shape in metabolic syndrome-induced cardiac remodeling remains unclear. This study determined the effect of pyridostigmine (PYR), which reversibly inhibits cholinesterase to improve autonomic imbalance, on high-fat diet (HFD)-induced cardiac insulin resistance and explored the potential effect on the shape of mitochondrial cristae...
January 8, 2019: Free Radical Biology & Medicine
Aliya M Lucatch, Darby J E Lowe, Rachel C Clark, Karolina Kozak, Tony P George
Purpose of review: To provide an overview of the underlying neurobiology of tobacco smoking in schizophrenia, and implications for treatment of this comorbidity. Recent findings: Explanations for heavy tobacco smoking in schizophrenia include pro-cognitive effects of nicotine, and remediation of the underlying pathophysiology of schizophrenia. Nicotine may ameliorate neurochemical deficits through nicotine acetylcholine receptors (nAChRs) located on the dopamine, glutamate, and GABA neurons. Neurophysiological indices including electroencephalography, electromyography, and smooth pursuit eye movement (SPEM) paradigms may be biomarkers for underlying neuronal imbalances that contribute to the specific risk of tobacco smoking initiation, maintenance, and difficulty quitting within schizophrenia...
2018: Frontiers in Psychiatry
Xin Wang, Zhaoxiang Meng, Jibing Wang, Hongyu Zhou, Yi Wu, Junfa Wu
Working memory impairment is a common cognitive dysfunction after traumatic brain injury (TBI), which severely affects the quality of life of patients. Acetylcholine is a neurotransmitter which is closely related to cognitive functions. In addition, epigenetic modifications are also related to cognitive functions. A neurorehabilitation strategy, enriched environment (EE) intervention, has been widely used to improve cognitive impairment. However, studies of the mechanism of EE on cholinergic system and epigenetic modifications in mouse with TBI have not been reported yet...
2018: PeerJ
Mahesh Ramalingam, Hyojung Kim, Yunjong Lee, Yun-Il Lee
The increasing lifespan in developed countries results in age-associated chronic diseases. Biological aging is a complex process associated with accumulated cellular damage by environmental or genetic factors with increasing age. Aging results in marked changes in brain structure and function. Age-related neurodegenerative diseases and disorders (NDDs) represent an ever-growing socioeconomic challenge and lead to an overall reduction in quality of life around the world. Alzheimer's disease (AD) and Parkinson's disease (PD) are most common degenerative neurological disorders of the central nervous system (CNS) in aging process...
2018: Frontiers in Aging Neuroscience
Krishnangsu Pradhan, Gaurav Das, Juhee Khan, Varsha Gupta, Surajit Barman, Anindyasundar Adak, Surajit Ghosh
Brain damage is associated with spatial imbalance of cholinergic system, which makes severe impact in recovery of damaged neurons of brain. Therefore, maintenance of cholinergic system is extremely important. Here, we fabricated an injectable hydrogel with acetylcholine-functionalized graphene oxide and poly(acrylic acid). Results revealed that this hydrogel is non-cytotoxic, promotes neurite outgrowth, stabilizes microtubule networks, and enhances the expression of some key neural markers in rat cortical primary neurons...
November 28, 2018: ACS Chemical Neuroscience
Jessica Sabbatine Chimini, Jose Sergio Possomato-Vieira, Maria Luiza Santos da Silva, Carlos A Dias-Junior
preeclampsia and hypertensive disorders of pregnancy are frequently associated with feto-placental growth restriction and that may be triggered by angiogenic imbalance and endothelial dysfunction. Impaired nitric oxide (NO) bioavailability seems to be involved in these pathophysiological changes observed in hypertensive pregnancy. Pravastatin has shown efficacy and to be safe during hypertension in pregnancy. However, NO involvement in pravastatin effects during maternal hypertension and feto-placental development is unclear...
October 14, 2018: Basic & Clinical Pharmacology & Toxicology
Chunxia Huang, John Man-Tak Chu, Yan Liu, Raymond Chuen-Chung Chang, Gordon Tin-Chun Wong
Postoperative cognitive dysfunction (POCD) occurs more frequently in elderly patients undergoing major surgery. Age associated cholinergic imbalance may exacerbate postoperative systemic and neuroinflammation, but the effect nicotinic acetylcholine receptor (nAchR) stimulation on the development of POCD remains unclear. Aged male C57BL/6N mice (18 months old) underwent a midline laparotomy or were exposed to sevoflurane anesthesia alone (4-5%), with or without concomitant varenicline, a partial nAchR, at 1 mg/kg/day...
December 2018: Neuropharmacology
Bijan Esmaeilnejad, Mousa Tavassoli, Awat Samiei, Nasser Hajipour, Abbas Imani-Baran, Farhad Farhang-Pajuh
This study was undertaken to assess the influence of an Anaplasma marginale infection on oxidative stress and antioxidant status, trace elements and cholinesterase as markers of the inflammatory process and biomarkers of oxidative imbalance. An infected group comprised of 35 crossbred Holstein cattle, about 2-3 years old, naturally infected with Anaplasma marginale, were divided into 4 subgroups according to their parasitemia rates (<1%, 1-10%, 10-20%, >20%) and also 10 healthy cattle as control were selected...
October 2018: Microbial Pathogenesis
Yiru Wang, Xia Shen
Postoperative delirium (POD) is a neurobehavioral syndrome caused by dysfunction of neural activity mainly in elderly people. POD is not uncommon, but under-recognized, and often serious. Multifactorial causes including aging, acetylcholine deficiency, sleep deprivation and intraoperative hypoxia have been proposed attempting to explain the processes leading to the development of POD. To date, however, no specific pathophysiologic mechanism has been identified. Here, we summarize the five most prominent theories (neuronal aging, neuroinflammation, neurotransmitter imbalance, neuroendocrine activation, and network connectivity change) to explain the development of delirium...
November 2018: Aging Clinical and Experimental Research
Juliana Tonietto Domingues, Carolinne Sayury Wajima, Patricia Acordi Cesconetto, Eduardo Benedetti Parisotto, Elisa Winkelmann-Duarte, Karin Dos Santos, Najla Saleh, Fabíola Branco Filippin-Monteiro, Guilherme Razzera, Fátima Regina Mena Barreto Silva, Regina Pessoa-Pureur, Ariane Zamoner
In this study, we used an experimental model of congenital hypothyroidism to show that deficient thyroid hormones (TH) disrupt different neurochemical, morphological and functional aspects in the cerebral cortex of 15-day-old offspring. Our results showing decreased glutamine synthetase (GS) activity and Ca2+ overload in the cerebral cortex of hypothyroid pups suggest misregulated glutamate metabolism associated with developmentally induced TH deficiency. The 14 C-MeAIB accumulation indicates upregulated System A activity and glutamine uptake by neurons...
July 18, 2018: Molecular and Cellular Endocrinology
Marwa Y Sallam, Sahar M El-Gowilly, Hanan M El-Gowelli, Mohammed A El-Lakany, Mahmoud M El-Mas
The cholinergic antiinflammatory pathway favorably influences end organ damage induced by inflammatory conditions. Here, we hypothesized that α7 and/or α4β2-nicotinic acetylcholine receptors (nAChRs) protect against cardiovascular and autonomic imbalances induced by endotoxemia in rats. We assessed dose-effect relationships of i.v. nicotine (25, 50, or 100 μg/kg), PHA-543613 (α7-nAChR agonist; 0.2 or 2.0 mg/kg), or 5-iodo-A-85380 (5IA, α4β2-nAChRs agonist; 0.01 or 0.1 mg/kg) on cardiovascular and inflammatory responses elicited by lipopolysaccharide (LPS, 10 mg/kg i...
September 5, 2018: European Journal of Pharmacology
Marta Toral, Miguel Romero, Alba Rodríguez-Nogales, Rosario Jiménez, Iñaki Robles-Vera, Francesca Algieri, Natalia Chueca-Porcuna, Manuel Sánchez, Néstor de la Visitación, Mónica Olivares, Federico García, Francisco Pérez-Vizcaíno, Julio Gálvez, Juan Duarte
SCOPE: The aim is to analyze whether the probiotic Lactobacillus fermentum CECT5716 (LC40) can prevent endothelial dysfunction and hypertension induced by tacrolimus in mice. METHODS AND RESULTS: Tacrolimus increases systolic blood pressure (SBP) and impairs endothelium-dependent relaxation to acetylcholine and these effects are partially prevented by LC40. Endothelial dysfunction induced by tacrolimus is related to both increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX2) and uncoupled endothelial nitric oxide synthase (eNOS)-driven superoxide production and Rho-kinase-mediated eNOS inhibition...
May 30, 2018: Molecular Nutrition & Food Research
Melissa M Conti, Nicole Chambers, Christopher Bishop
Traditionally, dopamine (DA) and acetylcholine (ACh) striatal systems were considered antagonistic and imbalances or aberrant signaling between these neurotransmitter systems could be detrimental to basal ganglia activity and pursuant motor function, such as in Parkinson's disease (PD) and L-DOPA-induced dyskinesia (LID). Herein, we discuss the involvement of cholinergic interneurons (ChIs) in striatally-mediated movement in a healthy, parkinsonian, and dyskinetic state. ChIs integrate numerous neurotransmitter signals using intrinsic glutamate, serotonin, and DA receptors and convey the appropriate transmission onto nearby muscarinic and nicotinic ACh receptors to produce movement...
September 2018: Neuroscience and Biobehavioral Reviews
Richard M Walsh, Soung-Hun Roh, Anant Gharpure, Claudio L Morales-Perez, Jinfeng Teng, Ryan E Hibbs
Fast chemical communication in the nervous system is mediated by neurotransmitter-gated ion channels. The prototypical member of this class of cell surface receptors is the cation-selective nicotinic acetylcholine receptor. As with most ligand-gated ion channels, nicotinic receptors assemble as oligomers of subunits, usually as hetero-oligomers and often with variable stoichiometries 1 . This intrinsic heterogeneity in protein composition provides fine tunability in channel properties, which is essential to brain function, but frustrates structural and biophysical characterization...
May 2018: Nature
Deniz Kantar Gok, Enis Hidisoglu, Guzide Ayse Ocak, Hakan Er, Alev Duygu Acun, Piraye Yargıcoglu
In the present study, we examined whether rosmarinic acid (RA) reverses amyloid β (Aβ) induced reductions in antioxidant defense, lipid peroxidation, cholinergic damage as well as the central auditory deficits. For this purpose, Wistar rats were randomly divided into four groups; Sham(S), Sham + RA (SR), Aβ42 peptide (Aβ) and Aβ42 peptide + RA (AβR) groups. Rat model of Alzheimer was established by bilateral injection of Aβ42 peptide (2,2 nmol/10 μl) into the lateral ventricles. RA (50 mg/kg, daily) was administered orally by gavage for 14 days after intracerebroventricular injection...
September 2018: Neurochemistry International
Yong Zhang, Xiao Jia, Yan Xia, Hao Li, Fei Chen, Jie Zhu, Xiuying Zhang, Yanyan Zhang, YuZhong Wang, Yanan Xu, Meng Pan, Xiaoyu Huang, Tingyan Yu, Linlin Fu, Chenghua Xiao, Deqin Geng
Previous studies have shown that interferon regulatory factor-4 (IRF4) and IRF8 play critical but distinct roles in the differentiation of B cells into plasma cells (PCs). In the present study, we aimed to measure the expression levels of IRF4 and IRF8 in B cells from patients with myasthenia gravis (MG) and to investigate whether the expression of IRF4 and IRF8 associates with pathogenesis of MG. A total of 35 anti-acetylcholine receptor (AChR) antibody (Ab)-positive patients with MG [20 generalized MG (GMG) and 15 ocular MG (OMG) and 25 healthy donors were recruited in this study...
May 2018: Autoimmunity
Sumit Jamwal, Puneet Kumar
Alteration in neurotransmitters signaling in basal ganglia has been consistently shown to significantly contribute to the pathophysiological basis of Parkinson's disease and Huntington's disease. Dopamine is important neurotransmitter which play critical role in coordinated body movements. Alteration in level of brain dopamine and receptor radically contribute to irregular movements, glutamate mediated excitotoxic neuronal death and further leads to imbalance in the levels of other neurotransmitters viz. GABA, adenosine, acetylcholine and endocannabinoids...
March 1, 2018: Current Neuropharmacology
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
Jose Adolfo Villegas, Jérôme Van Wassenhove, Rozen Le Panse, Sonia Berrih-Aknin, Nadine Dragin
A chronic autoimmune disease, myasthenia gravis (MG) is characterized in 85% of patients by antibodies directed against the acetylcholine receptor (AChR) located at the neuromuscular junction. The functional and effective balance between regulatory T cells (Treg cells) and effector T cells (Teff cells) is lost in the hyperplastic thymus of MG patients with antibodies specific for the AChR (AChR+ MG patients). The objective of this review is to describe how Treg cells and inflammatory T cells participate in this imbalance and contribute to induce a chronic inflammatory state in the MG thymus...
February 2018: Annals of the New York Academy of Sciences
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