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https://www.readbyqxmd.com/read/28187857/adaptive-and-behavioral-changes-in-kynurenine-3-monooxygenase-knockout-mice-relevance-to-psychotic-disorders
#1
Sophie Erhardt, Ana Pocivavsek, Mariaelena Repici, Xi-Cong Liu, Sophie Imbeault, Daniel C Maddison, Marian A R Thomas, Joshua L Smalley, Markus K Larsson, Paul J Muchowski, Flaviano Giorgini, Robert Schwarcz
BACKGROUND: Kynurenine 3-monooxygenase converts kynurenine to 3-hydroxykynurenine, and its inhibition shunts the kynurenine pathway-which is implicated as dysfunctional in various psychiatric disorders-toward enhanced synthesis of kynurenic acid, an antagonist of both α7 nicotinic acetylcholine and N-methyl-D-aspartate receptors. Possibly as a result of reduced kynurenine 3-monooxygenase activity, elevated central nervous system levels of kynurenic acid have been found in patients with psychotic disorders, including schizophrenia...
December 16, 2016: Biological Psychiatry
https://www.readbyqxmd.com/read/28179105/a-prenatal-nicotine-exposure-mouse-model-of-methylphenidate-responsive-adhd-associated-cognitive-phenotypes
#2
Jinmin Zhu, Fangfang Fan, Deirdre M McCarthy, Lin Zhang, Elisa N Cannon, Thomas J Spencer, Joseph Biederman, Pradeep G Bhide
Prenatal exposure to nicotine via cigarette smoke or other forms of tobacco use is a significant environmental risk factor for attention deficit hyperactivity disorder (ADHD). The neurobiological mechanisms underlying the link between prenatal nicotine exposure (PNE) and ADHD are not well understood. Animal models, especially rodent models, are beginning to bridge this gap in knowledge. Although ADHD is characterized by hyperactivity, inattention, impulsivity and working memory deficits, the majority of the animal models are based on only one or two ADHD associated phenotypes, in particular, hyperactivity or inattention...
February 4, 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28169167/design-and-synthesis-of-a-novel-series-of-4-heteroarylamino-1-azaspiro-oxazole-5-3-bicyclo-2-2-2-octanes-as-%C3%AE-7-nicotinic-receptor-agonists-2-development-of-4-heteroaryl-sar
#3
Christiana Iwuagwu, Dalton King, Ivar M McDonald, James Cook, F Christopher Zusi, Matthew D Hill, Robert A Mate, Haiquan Fang, Ronald Knox, Lizbeth Gallagher, Debra Post-Munson Amy Easton, Regina Miller, Yulia Benitex, Judy Siuciak, Nicholas Lodge, Robert Zaczek, Daniel Morgan, Linda Bristow, John E Macor, Richard E Olson
Quinuclidine-containing spirooxazolines, as described in the previous report in this series, were demonstrated to have utility as α7 nicotinic acetylcholine receptor (α7 nAChR) partial agonists. In this work, the SAR of this chemotype was expanded to include an array of diazine heterocyclic substitutions. Many of the heterocyclic analogs were potent partial agonists of the α7 receptor, selective against other nicotinic receptors and the serotinergic 5HT3A receptor. (1'S,3'R,4'S)-N-(6-phenylpyrimidin-4-yl)-4H-1'-azaspiro[oxazole-5,3'-bicyclo[2...
January 20, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28168926/stimulation-of-nicotinic-acetylcholine-alpha7-receptors-rescue-schizophrenia-like-cognitive-impairments-in-rats
#4
Agnieszka Potasiewicz, Agnieszka Nikiforuk, Małgorzata Hołuj, Piotr Popik
Alpha7 nicotinic acetylcholine receptor (α7 nAChR) dysfunction plays an important role in schizophrenia. Positive allosteric modulators of α7 nAChR have emerged as a promising therapeutic approach to manage cognitive deficits that are inadequately treated in schizophrenic patients. The aim of the present study was to evaluate the ability of type I (CCMI) and type II (PNU120596) α7 nAChR positive allosteric modulators to counteract MK-801-induced cognitive and sensorimotor gating deficits. The activity of these compounds was compared with the action of the α7 nAChR agonist A582941...
February 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28162919/cholinergic-receptor-binding-in-alzheimer-disease-and-healthy-aging-assessment-in-vivo-with-positron-emission-tomography-imaging
#5
David L Sultzer, Rebecca J Melrose, Hannah Riskin-Jones, Theresa A Narvaez, Joseph Veliz, Timothy K Ando, Kevin O Juarez, Dylan G Harwood, Arthur L Brody, Mark A Mandelkern
OBJECTIVE: To compare regional nicotinic cholinergic receptor binding in older adults with Alzheimer disease (AD) and healthy older adults in vivo and to assess relationships between receptor binding and clinical symptoms. METHODS: Using cross-sectional positron emission tomography (PET) neuroimaging and structured clinical assessment, outpatients with mild to moderate AD (N = 24) and healthy older adults without cognitive complaints (C group; N = 22) were studied...
January 4, 2017: American Journal of Geriatric Psychiatry
https://www.readbyqxmd.com/read/28161246/partial-agonism-at-the-%C3%AE-7-nicotinic-acetylcholine-receptor-improves-attention-impulsive-action-and-vigilance-in-low-attentive-rats
#6
Andrew Hayward, Lisa Adamson, Joanna C Neill
Inattention is a disabling symptom in conditions such as schizophrenia and attention deficit/hyperactivity disorder. Nicotine can improve attention and vigilance, but is unsuitable for clinical use due to abuse liability. Genetic knockout of the α7 nicotinic acetylcholine receptor (nAChR) induces attention deficits therefore selective agonism may improve attention, without the abuse liability associated with nicotine. The α7 nAChR partial agonist encenicline (formerly EVP-6124) enhances memory in rodents and humans...
February 1, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28146250/effect-of-selective-inhibition-of-reactivated-nicotine-associated-memories-with-propranolol-on-nicotine-craving
#7
Yan-Xue Xue, Jia-Hui Deng, Ya-Yun Chen, Li-Bo Zhang, Ping Wu, Geng-Di Huang, Yi-Xiao Luo, Yan-Ping Bao, Yu-Mei Wang, Yavin Shaham, Jie Shi, Lin Lu
Importance: A relapse into nicotine addiction during abstinence often occurs after the reactivation of nicotine reward memories, either by acute exposure to nicotine (a smoking episode) or by smoking-associated conditioned stimuli (CS). Preclinical studies suggest that drug reward memories can undergo memory reconsolidation after being reactivated, during which they can be weakened or erased by pharmacological or behavioral manipulations. However, translational clinical studies using CS-induced memory retrieval-reconsolidation procedures to decrease drug craving reported inconsistent results...
February 1, 2017: JAMA Psychiatry
https://www.readbyqxmd.com/read/28146243/effect-of-a-brief-memory-updating-intervention-on-smoking-behavior-a-randomized-clinical-trial
#8
Lisa J Germeroth, Matthew J Carpenter, Nathaniel L Baker, Brett Froeliger, Steven D LaRowe, Michael E Saladin
Importance: Recent research on addiction-related memory processes suggests that protracted extinction training following brief cue-elicited memory retrieval (ie, retrieval-extinction [R-E] training) can attenuate/eradicate the ability of cues to elicit learned behaviors. One study reported that cue-elicited craving among detoxified heroin addicts was substantially attenuated following R-E training and through 6-month follow-up. Objective: To build on these impressive findings by examining whether R-E training could attenuate smoking-related craving and behavior...
February 1, 2017: JAMA Psychiatry
https://www.readbyqxmd.com/read/28131771/the-ventral-hippocampal-muscarinic-cholinergic-system-plays-a-key-role-in-sexual-dimorphisms-of-spatial-working-memory-in-rats
#9
Brandon J Hall, Yael Abreu-Villaça, Marty Cauley, Shaqif Junaid, Hannah White, Abtin Kiany, Edward D Levin
Sex differences in cognitive processing and function have been documented in human and animal studies. Females have been found to perform better than males on non-spatial memory tasks, while males tend to outperform females on spatial memory tasks. The neural mechanisms underlying these sexual dimorphisms are unclear. However, it is known that the cholinergic system is critically involved in memory processes, and there are notable differences between males and females in cholinergic system function and receptor expression...
January 26, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28130648/short-and-long-term-effects-of-nicotine-and-the-histone-deacetylase-inhibitor-phenylbutyrate-on-novel-object-recognition-in-zebrafish
#10
M P Faillace, A Pisera-Fuster, M P Medrano, A C Bejarano, R O Bernabeu
RATIONALE: Zebrafish have a sophisticated color- and shape-sensitive visual system, so we examined color cue-based novel object recognition in zebrafish. We evaluated preference in the absence or presence of drugs that affect attention and memory retention in rodents: nicotine and the histone deacetylase inhibitor (HDACi) phenylbutyrate (PhB). OBJECTIVES: The objective of this study was to evaluate whether nicotine and PhB affect innate preferences of zebrafish for familiar and novel objects after short- and long-retention intervals...
January 27, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28126277/weight-of-evidence-evaluation-of-a-network-of-adverse-outcome-pathways-linking-activation-of-the-nicotinic-acetylcholine-receptor-in-honey-bees-to-colony-death
#11
REVIEW
Carlie A LaLone, Daniel L Villeneuve, Judy Wu-Smart, Rebecca Y Milsk, Keith Sappington, Kristina V Garber, Justin Housenger, Gerald T Ankley
Ongoing honey bee (Apis mellifera) colony losses are of significant international concern because of the essential role these insects play in pollinating crops. Both chemical and non-chemical stressors have been implicated as possible contributors to colony failure; however, the potential role(s) of commonly-used neonicotinoid insecticides has emerged as particularly concerning. Neonicotinoids act on the nicotinic acetylcholine receptors (nAChRs) in the central nervous system to eliminate pest insects. However, mounting evidence indicates that neonicotinoids also may adversely affect beneficial pollinators, such as the honey bee, via impairments on learning and memory, and ultimately foraging success...
January 24, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28105289/development-of-4-heteroarylamino-1-azaspiro-oxazole-5-3-bicyclo-2-2-2-octanes-as-%C3%AE-7-nicotinic-receptor-agonists
#12
Matthew D Hill, Haiquan Fang, H Dalton King, Christiana I Iwuagwu, Ivar M McDonald, James Cook, F Christopher Zusi, Robert A Mate, Ronald J Knox, Debra Post-Munson, Amy Easton, Regina Miller, Kimberley Lentz, Wendy Clarke, Yulia Benitex, Nicholas Lodge, Robert Zaczek, Rex Denton, Daniel Morgan, Linda Bristow, John E Macor, Richard Olson
We describe the synthesis of quinuclidine-containing spiroimidates and their utility as α7 nicotinic acetylcholine receptor (nAChR) partial agonists. A convergent synthetic route allowed for rapid SAR investigation and provided a diverse set of fused 6,5-heteroaryl analogs. Two potent and selective α7 nAChR partial agonists, (1'S,3'R,4'S)-N-(7-bromopyrrolo[2,1-f][1,2,4]triazin-4-yl)-4H-1'-azaspiro[oxazole-5,3'-bicyclo[2.2.2]octan]-2-amine (20) and (1'S,3'R,4'S)-N-(7-chloropyrrolo[2,1-f][1,2,4]triazin-4-yl)-4H-1'-azaspiro[oxazole-5,3'-bicyclo[2...
January 12, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28101715/cortex-and-amygdala-dependent-learning-and-nicotinic-acetylcholine-receptor-gene-expression-is-severely-impaired-in-mice-orally-treated-with-alcl3
#13
Syeda Mehpara Farhat, Aamra Mahboob, Touqeer Ahmed
Recent industrialization has increased human exposure to bio-available aluminum (Al). If more Al enters the brain than leaves, Al concentration will rise in the brain leading to neurodegenerative disorders. The aim of the present study was to determine Al concentration, neurodegeneration, and nicotinic acetylcholine receptor (nAChR) gene expression in the cortex and amygdala after oral ingestion of Al salt. The effect of Al on cortex- and amygdala-dependent learning and memory functions was also assessed. Mice were given AlCl3 (250 mg/kg) in drinking water for 42 days...
January 18, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28078612/ameliorative-effect-of-ginsenoside-rg1-on-lipopolysaccharide-induced-cognitive-impairment-role-of-cholinergic-system
#14
Yang Jin, Jian Peng, Xiaona Wang, Dong Zhang, Tianyin Wang
Bacterial endotoxin lipopolysaccharide (LPS) can induce systemic inflammation, and therefore disrupt learning and memory processes. Ginsenoside Rg1, a major bioactive component of ginseng, is shown to greatly improve cognitive function. The present study was designed to further investigate whether administration of ginsenoside Rg1 can ameliorate LPS-induced cognitive impairment in the Y-maze and Morris water maze (MWM) task, and to explore the underlying mechanisms. Results showed that exposure to LPS (500 μg/kg) significantly impaired working and spatial memory and that repeated treatment with ginsenoside Rg1 (200 mg/kg/day, for 30 days) could effectively alleviate the LPS-induced cognitive decline as indicated by increased working and spatial memory in the Y-maze and MWM tests...
January 11, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28049400/elucidating-treatment-of-alzheimer-s-disease-via-different-receptors
#15
Badar Ul Islam, Mohd Shahnawaz Khan, Nasimudeen R Jabir, Mohammad Amjad Kamal, Shams Tabrez
Alzheimer's disease (AD) is an irreversible multifaceted neurodegenerative disorder that gradually degrades neuronal cells. Presently, it is the most common reason for the memory loss and dementia in older individuals. It is patho-physiologically described by extracellular amyloid beta (Aβ) deposition, intracellular neurofibrillary tangles (NFTs) retention, neuronal decline, and neurotransmitter system derangement. Various receptors such as nicotinic acetylcholine, N-methyl-D-aspartate, insulin, serotonin, adenosine, and histamine are actively involved in the physiological progression of AD...
January 3, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28049095/riluzole-ameliorates-learning-and-memory-deficits-in-a%C3%AE-25-35-induced-rat-model-of-alzheimer-s-disease-and-is-independent-of-cholinoceptor-activation
#16
Zahra Mokhtari, Tourandokht Baluchnejadmojarad, Farnaz Nikbakht, Monireh Mansouri, Mehrdad Roghani
Alzheimer's disease (AD) is a major global public health concern and social care problem that is associated with learning, memory, and cognitive deficits. Riluzole is a glutamate modulator which has shown to improve memory performance in aged rats and may be of benefit in Alzheimer's disease. In the present study, its beneficial effect on attenuation of learning and memory deficits in Aβ25-35-induced rat model of AD was assessed. Riluzole administration at a dose of 10mg/kg/day p.o. improved spatial memory in Morris water maze and retention and recall in passive avoidance task and its protective effect was not neutralized following intracerebroventricular microinjection of muscarinic or nicotinic receptor antagonists...
March 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28045139/chrna7-deficient-mice-manifest-no-consistent-neuropsychiatric-and-behavioral-phenotypes
#17
Jiani Yin, Wu Chen, Hongxing Yang, Mingshan Xue, Christian P Schaaf
The alpha7 nicotinic acetylcholine receptor, encoded by the CHRNA7 gene, has been implicated in various psychiatric and behavioral disorders, including schizophrenia, bipolar disorder, epilepsy, autism, Alzheimer's disease, and Parkinson's disease, and is considered a potential target for therapeutic intervention. 15q13.3 microdeletion syndrome is a rare genetic disorder, caused by submicroscopic deletions on chromosome 15q. CHRNA7 is the only gene in this locus that has been deleted entirely in cases involving the smallest microdeletions...
January 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28029335/enhanced-susceptibility-of-ca3-hippocampus-to-prenatal-nicotine-exposure
#18
O O Kalejaiye, M C Gondré-Lewis
The brain is highly susceptible to adverse effects of drugs of abuse during early phases of life. Prenatal nicotine exposure (PNE), a preventable cause of gestational and infant mortality, can alter neuron wiring and induce sustained deficits in attention and learning. Here, a rat model of PNE (embryonic days 7-21) was used to examine the maturing hippocampus, which encodes new memories and processes emotional memory. Components of synaptic signaling were evaluated at postnatal day 14 (P14), a period of prolific synaptogenesis in rats, to determine if glutamatergic transmission-associated molecules are regulated in subregions of hippocampus as early as P14...
December 28, 2016: Journal of Developmental Origins of Health and Disease
https://www.readbyqxmd.com/read/28025093/varenicline-improves-motor-and-cognitive-deficits-and-decreases-depressive-like-behaviour-in-late-stage-yac128-mice
#19
Ailsa L McGregor, Gary D'Souza, Donghyo Kim, Malcolm D Tingle
OBJECTIVE: Studies in the post mortem human brain and in genetic mouse model suggest that dysfunctional cholinergic neurotransmission, through a loss of agonist rather than receptors may be a significant contributing factor to HD pathology. If correct, pharmacological replacement may therefore be a potential treatment strategy. We have investigated whether chronic administration of the selective nicotinic partial agonist varenicline improved motor, cognitive and affective symptoms in a transgenic mouse model of Huntington's disease...
December 23, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/28004072/-temporal-and-spatial-changes-of-%C3%AE-7nachr-and-nnos-in-cerebral-cortex-and-hippocampus-of-a%C3%AE-induced-cognitive-dysfunction-rats
#20
Yan-Li Wang, Li-Xia Liu, Shao-Hu Wang, Wen-Xiu Qi
The present study was to explore the temporal and spatial distributions and variations of α7 nicotinic acetylcholine receptor (α7nAChR) and neuronal nitric oxide synthetase (nNOS) in cerebral cortex and hippocampus of Aβ-induced cognitive dysfunction rats. Sixty Sprague-Dawley (SD) rats were randomly divided into six groups. Three experimental groups were intracerebroventricularly (i.c.v.) injected with condensed-amyloid beta peptides 1-42 (Aβ1-42, 2.5 µg/µL, 4 µL) and were observed on day 7 (7 d Aβ group), day 14 (14 d Aβ group) and day 21 (21 d Aβ group), respectively...
December 25, 2016: Sheng Li Xue Bao: [Acta Physiologica Sinica]
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