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https://www.readbyqxmd.com/read/28724203/huprine-x-attenuates-the-neurotoxicity-induced-by-kainic-acid-especially-brain-inflammation
#1
J Relat, B Pérez, P Camps, D Muñoz-Torrero, A Badia, M V Clos
Huprine X (HX) is a synthetic anticholinesterasic compound that exerts a potent inhibitory action on acetylcholinesterase (AChE) activity, an agonist effect on cholinergic receptors, neuroprotective activity in different neurotoxicity models in vivo and in vitro and cognition enhancing effects in non-transgenic (C57BL/6) and transgenic (3xTg-AD, APPswe) mice. In the present study, we assessed the ability of HX (0.8 mg/kg, 21 days) to prevent the damage induced by kainic acid (KA; 28 mg/kg) regarding apoptosis, glia reactivity and neurogenesis in mouse brain...
July 19, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28722769/promoter-iv-bdnf-deficiency-disturbs-cholinergic-gene-expression-of-chrna5-chrm2-and-chrm5-effects-of-drug-and-environmental-treatments
#2
Kazuko Sakata, Abigail E Overacre
Brain-derived neurotrophic factor (BDNF) promotes maturation of cholinergic neurons. However, how activity-dependent BDNF expression affects specific cholinergic gene expression remains unclear. This study addressed this question by determining mRNA levels of 22 acetylcholine receptor subunits, the choline transporter (CHT), and the choline acetyltransferase (ChAT) in mice deficient in activity-dependent BDNF via promoter IV (KIV) and control wild-type mice. Quantitative RT-PCR revealed significant reductions in nicotinic acetylcholine receptor alpha 5 (CHRNA5) in the frontal cortex and hippocampus and M5 muscarinic acetylcholine receptor (CHRM5) in the hippocampus, but significant increases in M2 muscarinic acetylcholine receptor (CHRM2) in the frontal cortex of KIV mice compared to wild-type mice...
July 19, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28721035/intracellular-interactions-of-umeclidinium-and-vilanterol-in-human-airway-smooth-muscle
#3
Nooreen Shaikh, Malcolm Johnson, David A Hall, Kian Fan Chung, John H Riley, Sally Worsley, Pankaj K Bhavsar
BACKGROUND: Intracellular mechanisms of action of umeclidinium (UMEC), a long-acting muscarinic receptor antagonist, and vilanterol (VI), a long-acting β2-adrenoceptor (β2R) agonist, were investigated in target cells: human airway smooth-muscle cells (ASMCs). MATERIALS AND METHODS: ASMCs from tracheas of healthy lung-transplant donors were treated with VI, UMEC, UMEC and VI combined, or control compounds (salmeterol, propranolol, ICI 118.551, or methacholine [MCh])...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/28720796/eeg-machine-learning-for-accurate-detection-of-cholinergic-intervention-and-alzheimer-s-disease
#4
Sonja Simpraga, Ricardo Alvarez-Jimenez, Huibert D Mansvelder, Joop M A van Gerven, Geert Jan Groeneveld, Simon-Shlomo Poil, Klaus Linkenkaer-Hansen
Monitoring effects of disease or therapeutic intervention on brain function is increasingly important for clinical trials, albeit hampered by inter-individual variability and subtle effects. Here, we apply complementary biomarker algorithms to electroencephalography (EEG) recordings to capture the brain's multi-faceted signature of disease or pharmacological intervention and use machine learning to improve classification performance. Using data from healthy subjects receiving scopolamine we developed an index of the muscarinic acetylcholine receptor antagonist (mAChR) consisting of 14 EEG biomarkers...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720379/inhibition-of-12-15-lox-ameliorates-cognitive-and-cholinergic-dysfunction-in-mouse-model-of-hypobaric-hypoxia-via-attenuation-of-oxidative-nitrosative-stress
#5
Richa Choudhary, Udayabanu Malairaman, Anju Katyal
12/15 Lipoxygenase has recently been described as potent propagator of oxidative stress and is closely associated with cognitive decline in neurodegenerative diseases. The mechanism/s behind 12/15 LOX involvement in cognitive deficits remain obscure. The current study has been designed to investigate the underlying role of 12/15LOX and effect of 12/15 LOX inhibition on hypobaric hypoxia induced memory impairment and cholinergic deficits. Male Balb/c mice subjected to simulated hypobaric hypoxia/reoxygenation condition for 3 days showed marked working memory impairment concomitant with hippocampal neuronal damage and malondialdehyde production which were significantly attenuated by baicalein, a specific inhibitor of 12/15LOX...
July 15, 2017: Neuroscience
https://www.readbyqxmd.com/read/28720101/drug-candidates-in-clinical-trials-for-alzheimer-s-disease
#6
REVIEW
Shih-Ya Hung, Wen-Mei Fu
Alzheimer's disease (AD) is a major form of senile dementia, characterized by progressive memory and neuronal loss combined with cognitive impairment. AD is the most common neurodegenerative disease worldwide, affecting one-fifth of those aged over 85 years. Recent therapeutic approaches have been strongly influenced by five neuropathological hallmarks of AD: acetylcholine deficiency, glutamate excitotoxicity, extracellular deposition of amyloid-β (Aβ plague), formation of intraneuronal neurofibrillary tangles (NTFs), and neuroinflammation...
July 19, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28716723/pharmacological-characterization-of-the-interaction-between-umeclidinium-and-vilanterol-in-human-bronchi
#7
Luigino Calzetta, Paola Rogliani, Francesco Facciolo, Erino Rendina, Mario Cazzola, Maria Gabriella Matera
The long-acting β2-agonist (LABA) / long-acting muscarinic antagonist (LAMA) fixed dose combination (FDC) therapy represents the cornerstone for the treatment of chronic obstructive pulmonary disease (COPD). Nevertheless, conflicting clinical findings still exist on the real benefit of the LABA/LAMA FDCs. Therefore, we investigated whether combining the LABA vilanterol with the LAMA umeclidinium may induce synergistic bronchorelaxant effect in isolated airways. The effect of umeclidinium and vilanterol, administered alone, in combination at the ratio of concentrations reproducing the doses delivered by Anoro(®) Ellipta(®) (55:22), or at isoeffective low concentrations, was investigated on the cholinergic contractile tone induced by the parasympathetic activation of human isolated airways...
July 14, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28716235/psychosis-in-parkinson-s-disease-from-the-soft-signs-to-the-hard-science
#8
REVIEW
Abhishek Lenka, Priyantha Herath, Rita Christopher, Pramod Kumar Pal
Patients with Parkinson's disease (PD) may develop a wide spectrum of non-motor symptoms during the course of illness. Psychosis is one such commonly observed non-motor symptoms of PD. Although several studies based on neuroimaging, genetics, retinal imaging, and neuropsychological evaluations have explored the pathogenesis of psychosis in PD; exact neural correlates are yet to be understood. Identification of factors related to psychosis in PD is important, as psychosis has been reported to be associated with higher rates of mortality, caregiver distress, and nursing home placements...
August 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28714717/acetylcholine-contributes-to-the-integration-of-self-movement-cues-in-head-direction-cells
#9
Ryan M Yoder, Jeremy H M Chan, Jeffrey S Taube
Acetylcholine contributes to accurate performance on some navigational tasks, but details of its contribution to the underlying brain signals are not fully understood. The medial septal area provides widespread cholinergic input to various brain regions, but selective damage to medial septal cholinergic neurons generally has little effect on landmark-based navigation, or the underlying neural representations of location and directional heading in visual environments. In contrast, the loss of medial septal cholinergic neurons disrupts navigation based on path integration, but no studies have tested whether these path integration deficits are associated with disrupted head direction (HD) cell activity...
August 2017: Behavioral Neuroscience
https://www.readbyqxmd.com/read/28714396/differential-effects-of-nicotine-exposure-on-the-hippocampus-across-lifespan
#10
Dana Zeid, Munir Gunes Kutlu, Thomas J Gould
Nicotine exposure affects the hippocampus through activation of hippocampal nicotinic acetylcholine receptors (nAChRs), which are present throughout excitatory and inhibitory hippocampal circuitry. The role of cholinergic functioning in the hippocampus varies across developmental stages so that nicotine exposure differentially affects this region depending upon timing of exposure, producing developmentally distinct changes in structure, function, and behavior. The hippocampus continues to mature well into adolescence, and this development is modulated by cholinergic activity...
July 13, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28714277/free-fatty-acid-receptor-3-activation-suppresses-neurogenic-motility-in-rat-proximal-colon
#11
I Kaji, Y Akiba, T Furuyama, D W Adelson, K Iwamoto, M Watanabe, A Kuwahara, J D Kaunitz
BACKGROUND: Short-chain fatty acids (SCFA) are microbial fermentation products absorbed by the colon. We recently reported that activation of the SCFA receptor termed free fatty acid receptor 3 (FFA3), expressed on cholinergic nerves, suppresses nicotinic acetylcholine receptor (nAChR)-mediated transepithelial anion secretion. This study aimed to clarify how activation of neurally expressed FFA3 affects colonic motor function. METHODS: FFA3-expressing myenteric neurons were identified by immunostaining; contractions of isolated circular muscle strips obtained from rat proximal colon were measured by isometric transducers...
July 17, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28713248/deep-brain-magnetic-stimulation-promotes-neurogenesis-and-restores-cholinergic-activity-in-a-transgenic-mouse-model-of-alzheimer-s-disease
#12
Junli Zhen, Yanjing Qian, Jian Fu, Ruijun Su, Haiting An, Wei Wang, Yan Zheng, Xiaomin Wang
Alzheimer's disease (AD) is characterized by progressive decline of memory and cognitive functions. Deep magnetic stimulation (DMS), a noninvasive and nonpharmacological brain stimulation, has been reported to alleviate stress-related cognitive impairment in neuropsychiatric disorders. Our previous study also discovered the preventive effect of DMS on cognitive decline in an AD mouse model. However, the underlying mechanism must be explored further. In this study, we investigated the effect of DMS on spatial learning and memory functions, neurogenesis in the dentate gyrus (DG), as well as expression and activity of the cholinergic system in a transgenic mouse model of AD (5XFAD)...
2017: Frontiers in Neural Circuits
https://www.readbyqxmd.com/read/28711697/role-of-muscarinic-receptors-in-the-contraction-of-jejunal-smooth-muscle-in-the-horse-an-in-vitro-study
#13
Alessandro Menozzi, Cristina Pozzoli, Enzo Poli, Giada Bontempi, Paolo Serventi, Valentina Meucci, Luigi Intorre, Simone Bertini
Nonselective antimuscarinic drugs are clinically useful in several pathologic conditions of horses, but, blocking all muscarinic receptor (MR) subtypes, may cause several side effects. The availability of selective antimuscarinic drugs could improve therapeutic efficacy and safety. We aimed to enlighten the role of different MR subtypes by evaluating the effects of nonselective, and selective M1, M2 and M3 MR antagonists on the contractions of horse jejunum. Segments of circular muscle of equine jejunum, were put into organ baths, connected to isotonic transducers, and the effects on ACh concentration-response curves, and on electrical field stimulation (EFS)-evoked contractions of intestinal preparations, induced by nonselective or selective MR antagonists, compared to pre-drug level, were studied...
July 11, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28710881/an-ethanolic-extract-of-desmodium-adscendens-exhibits-antipsychotic-like-activity-in-mice
#14
Patrick Amoateng, Samuel Adjei, Dorcas Osei-Safo, Kennedy K E Kukuia, Thomas K Karikari, Alexander K Nyarko
BACKGROUND: Desmodium adscendens extract (DAE) is used traditionally in Ghana for the management of psychosis. The present study aimed at providing pharmacological evidence for its ethnomedical use by testing the hypothesis that an ethanolic extract of Desmodium adscendens may possess antipsychotic properties. METHODS: The primary behavioral effects of DAE on the central nervous system of mice were investigated using Irwin's test paradigm. Novelty-induced and apomorphine-induced locomotor and rearing behaviors in mice were explored in an open-field observational test system...
July 15, 2017: Journal of Basic and Clinical Physiology and Pharmacology
https://www.readbyqxmd.com/read/28709847/topographical-projections-from-the-nucleus-basalis-magnocellularis-meynert-to-the-frontal-cortex-a-voltage-sensitive-dye-imaging-study-in-rats
#15
Kazuaki Nagasaka, Yumiko Watanabe, Ichiro Takashima
BACKGROUND: The nucleus basalis magnocellularis/Meynert (NBM) has been explored as a new target for deep brain stimulation for neurological disorders. Although anatomical studies suggest the existence of cholinergic topographical projections of the NBM, it is still unknown whether NBM subregions differentially activate the frontal cortex. OBJECTIVE: To investigate the topography between the NBM and frontal cortex. METHODS: Electrical stimulation was applied to the anterior and posterior sites of the NBM in rats, and the evoked frontal activity was investigated using voltage-sensitive dye (VSD) imaging...
July 3, 2017: Brain Stimulation
https://www.readbyqxmd.com/read/28707074/presenilin-1-delta-e9-mutant-induces-stim1-driven-store-operated-calcium-channel-hyperactivation-in-hippocampal-neurons
#16
Maria Ryazantseva, Anna Goncharova, Kseniia Skobeleva, Maksim Erokhin, Axel Methner, Pavel Georgiev, Elena Kaznacheyeva
Presenilins regulate calcium homeostasis in the endoplasmic reticulum, and dysregulation of intracellular calcium has been implicated in the pathogenesis of Alzheimer disease. Elevated presenilin-1 (PS1) holoprotein levels have been detected in postmortem brains of patients carrying familial Alzheimer disease (FAD) PS1 mutations. This study examines the effect of the FAD presenilin mutant that lacks the ninth exon (PS1 ∆E9) and does not undergo endoproteolysis on store-operated calcium (SOC) entry. Significant enhancement of SOC channel activation was detected by electrophysiological measurements in hippocampal neurons with PS1 ∆E9 mutant expression...
July 13, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28704107/asthma-medication-use-among-adults-with-current-asthma-by-work-related-asthma-status-asthma-call-back-survey-29-states-2012-2013
#17
Katelynn E Dodd, Jacek M Mazurek
OBJECTIVE: Asthma severity is defined as the intensity of treatment required to achieve good control of asthma symptoms. Studies have shown that work-related asthma (WRA) can be associated with poorer asthma control and more severe symptoms than non-WRA. Associations between asthma medications and WRA status were assessed using data from the 2012-2013 Asthma Call-back Survey among ever-employed adults (≥18 years) with current asthma from 29 states. METHODS: Persons with WRA had been told by a physician that their asthma was work-related...
July 13, 2017: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/28702935/vitamin-d3-attenuates-cognitive-deficits-and-neuroinflammatory-responses-in-icv-stz-induced-sporadic-alzheimer-s-disease
#18
P Yamini, R S Ray, Kanwaljit Chopra
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by intracellular neurofibrillary tangles and extracellular Aβ deposition. Growing experimental evidence indicate diverse biological effects of vitamin D3 including antioxidant, neuroprotective, anti-inflammatory and cardiovascular benefits. However, the underlying neuroprotective mechanism of vitamin D3 is still largely elusive. Therefore, the present study was aimed to investigate the neuroprotective effects of vitamin D3 on ICV-STZ induced sporadic AD...
July 12, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28701543/novel-channel-mediated-choline-transport-in-cholinergic-neurons-of-the-mouse-retina
#19
Toshiyuki Ishii, Kohei Homma, Asuka Mano, Takumi Akagi, Yasuhide Shigematsu, Yukio Shimoda, Hiroyoshi Inoue, Yoshihiko Kakinuma, Makoto Kaneda
Choline uptake into the presynaptic terminal of cholinergic neurons is mediated by the high affinity choline transporter and is essential for acetylcholine synthesis. In a previous study, we reported that P2X2 purinoceptors are selectively expressed in OFF-cholinergic amacrine cells of the mouse retina. Under specific conditions, P2X2 purinoceptors acquire permeability to large cations, such as N-methyl-D-glucamine, and therefore potentially could act as a non-canonical pathway for choline entry into neurons...
July 12, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28700094/regulation-of-synaptic-acetylcholine-concentrations-by-acetylcholine-transport-in-rat-striatal-cholinergic-transmission
#20
Ikunobu Muramatsu, Junsuke Uwada, Takayoshi Masuoka, Hatsumi Yoshiki, Kiyonao Sada, Kung-Shing Lee, Matomo Nishio, Takaharu Ishibashi, Takanobu Taniguchi
In addition to hydrolysis by acetylcholine esterase (AChE), acetylcholine (ACh) is also directly taken up into brain tissues. In the present study, we examined whether the uptake of ACh is involved in the regulation of synaptic ACh concentrations. Superfusion experiments with rat striatal segments pre-incubated with [(3) H]choline were performed using an ultra-mini superfusion vessel, which was developed to minimize superfusate retention within the vessel. Hemicholinium-3 (HC-3) at concentrations less than 1 μM, selectively inhibited the uptake of [(3) H]choline by the high affinity-choline transporter 1 (CHT1) and had no effect on basal and electrically evoked [(3) H]efflux in superfusion experiments...
July 12, 2017: Journal of Neurochemistry
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