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https://www.readbyqxmd.com/read/28529765/signals-of-vagal-circuits-engaging-with-akt1-in-%C3%AE-7-nachr-cd11b-cells-lessen-e-coli-and-lps-induced-acute-inflammatory-injury
#1
Caiqi Zhao, Xi Yang, Emily M Su, Yuanyuan Huang, Ling Li, Michael A Matthay, Xiao Su
Vagal circuits-α7 nAChR (α7 nicotinic acetylcholine receptor, coded by Chrna7) signaling utilizes spleen as a hub to dampen systemic inflammatory responses. Vagal innervations also extend to the distal airways and alveoli. Vagotomy and deficiency of α7 nAChR deteriorate E. coli and lipopolysaccharide (LPS)-induced acute lung inflammatory responses; however, the underlying mechanisms remain elusive. Here, we hypothesized that vagal circuits would limit splenic release and lung recruitment of α7 nAChR(+)CD11b(+) cells (CD11b is coded by Itgam, a surface marker of monocytes and neutrophils) via phosphorylation of AKT1 and that this process would define the severity of lung injury...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28494468/genes-involved-in-neurodevelopment-neuroplasticity-and-bipolar-disorder-cacna1c-chrna1-and-mapk1
#2
Marco Calabrò, Laura Mandelli, Concetta Crisafulli, Antonella Sidoti, Tae-Youn Jun, Soo-Jung Lee, Changsu Han, Ashwin A Patkar, Prakash S Masand, Chi-Un Pae, Alessandro Serretti
BACKGROUND: Bipolar disorder (BPD) is a common and severe mental disorder. The involvement of genetic factors in the pathophysiology of BPD is well known. In the present study, we tested the association of several single-nucleotide polymorphisms (SNPs) within 3 strong candidate genes (CACNA1C, CHRNA7, and MAPK1) with BPD. These genes are involved in monoamine-related pathways, as well as in dendrite development, neuronal survival, synaptic plasticity, and memory/learning. METHODS: One hundred and thirty-two subjects diagnosed with BPD and 326 healthy controls of Korean ancestry were genotyped for 40 SNPs within CACNA1C, CHRNA17, and MAPK1...
2016: Neuropsychobiology
https://www.readbyqxmd.com/read/28371330/a-de-novo-deletion-in-a-boy-with-cerebral-palsy-suggests-a-refined-critical-region-for-the-4q21-22-microdeletion-syndrome
#3
Mehdi Zarrei, Daniele Merico, Barbara Kellam, Worrawat Engchuan, Tara Scriver, Rikash Jokhan, Michael D Wilson, Jeremy Parr, Edmond G Lemire, Dimitri J Stavropoulos, Stephen W Scherer
We present an 18-year-old boy with cerebral palsy, intellectual disability, speech delay, and seizures. He carries a likely pathogenic 1.3 Mb de novo heterozygous deletion in the 4q21.22 microdeletion syndrome region. He also carries a 436 kb maternally-inherited duplication impacting the first three exons of CHRNA7. The majority of previously published cases with 4q21.22 syndrome shared common features including growth restriction, muscular hypotonia, and absent or severely delayed speech. Using copy number variation (CNV) data available for other subjects, we defined a minimal critical region of 170...
May 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28345786/a-de-novo-nonsense-mutation-in-zbtb18-plus-a-de-novo-15q13-3-microdeletion-in-a-6-year-old-female
#4
Nadja Ehmke, Sylvio Karge, Johannes Buchmann, Dirk Korinth, Denise Horn, Olaf Reis, Frank Häßler
ZBTB18 has been proposed as candidate gene for microcephaly and abnormalities of the corpus callosum based on overlapping microdeletions of 1q43q44. More recently, de novo mutations of ZBTB18 have been identified in patients with syndromic and non-syndromic intellectual disability. Heterozygous microdeletions of 15q13.3 encompassing the candidate gene CHRNA7 are associated with developmental delay or intellectual disability with speech problems, hypotonia, and seizures. They are characterized by significant variability and reduced penetrance...
May 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28288124/c1-neurons-mediate-a-stress-induced-anti-inflammatory-reflex-in-mice
#5
Chikara Abe, Tsuyoshi Inoue, Mabel A Inglis, Kenneth E Viar, Liping Huang, Hong Ye, Diane L Rosin, Ruth L Stornetta, Mark D Okusa, Patrice G Guyenet
C1 neurons, located in the medulla oblongata, mediate adaptive autonomic responses to physical stressors (for example, hypotension, hemorrhage and presence of lipopolysaccharides). We describe here a powerful anti-inflammatory effect of restraint stress, mediated by C1 neurons: protection against renal ischemia-reperfusion injury. Restraint stress or optogenetic C1 neuron (C1) stimulation (10 min) protected mice from ischemia-reperfusion injury (IRI). The protection was reproduced by injecting splenic T cells that had been preincubated with noradrenaline or splenocytes harvested from stressed mice...
May 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28283678/deficiency-of-%C3%AE-7-nicotinic-acetylcholine-receptor-attenuates-bleomycin-induced-lung-fibrosis-in-mice
#6
Peiyu Sun, Ling Li, Caiqi Zhao, Mengyao Pan, Zhikang Qian, Xiao Su
α7 nicotinic acetylcholine receptor (α7 nAChR, coded by Chrna7) is indispensible in dampening proinflammatory responses. However, whether α7 nAChR would play a role in regulating bleomycin (BLM)-induced lung fibrosis is less investigated. Here, we intratracheally challenged wildtype and Chrna7(-/-) mice with BLM to elicit lung fibrosis. Taken advantage of this model, we measured body weight loss, lung fibrogenic genes (Acta2, Col1a1, Fsp1, and Fstl1), histology, Masson's trichrome staining, hydroxyproline levels, and expression of α-SMA at protein levels in the BLM-challenged lung for evaluating severity of lung fibrosis...
March 6, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28264500/geneanalytics-pathway-analysis-and-genetic-overlap-among-autism-spectrum-disorder-bipolar-disorder-and-schizophrenia
#7
Naveen S Khanzada, Merlin G Butler, Ann M Manzardo
Bipolar disorder (BPD) and schizophrenia (SCH) show similar neuropsychiatric behavioral disturbances, including impaired social interaction and communication, seen in autism spectrum disorder (ASD) with multiple overlapping genetic and environmental influences implicated in risk and course of illness. GeneAnalytics software was used for pathway analysis and genetic profiling to characterize common susceptibility genes obtained from published lists for ASD (792 genes), BPD (290 genes) and SCH (560 genes). Rank scores were derived from the number and nature of overlapping genes, gene-disease association, tissue specificity and gene functions subdivided into categories (e...
February 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28168676/erratum-to-the-cognitive-and-behavioral-phenotypes-of-individuals-with-chrna7-duplications
#8
M A Gillentine, L N Berry, R P Goin-Kochel, M A Ali, J Ge, D Guffey, J A Rosenfeld, V Hannig, P Bader, M Proud, M Shinawi, B H Graham, A Lin, S R Lalani, J Reynolds, M Chen, T Grebe, C G Minard, P Stankiewicz, A L Beaudet, C P Schaaf
No abstract text is available yet for this article.
February 6, 2017: Journal of Autism and Developmental Disorders
https://www.readbyqxmd.com/read/28058793/effects-of-selection-for-ethanol-preference-on-gene-expression-in-the-nucleus-accumbens-of-hs-cc-mice
#9
A M Colville, O D Iancu, D L Oberbeck, P Darakjian, C L Zheng, N A R Walter, C A Harrington, R P Searles, S McWeeney, R J Hitzemann
Previous studies on changes in murine brain gene expression associated with the selection for ethanol preference have used F2 intercross or heterogeneous stock (HS) founders, derived from standard laboratory strains. However, these populations represent only a small proportion of the genetic variance available in Mus musculus. To investigate a wider range of genetic diversity, we selected mice for ethanol preference using an HS derived from the eight strains of the collaborative cross. These HS mice were selectively bred (four generations) for high and low ethanol preference...
April 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28045139/chrna7-deficient-mice-manifest-no-consistent-neuropsychiatric-and-behavioral-phenotypes
#10
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/27853923/the-cognitive-and-behavioral-phenotypes-of-individuals-with-chrna7-duplications
#11
M A Gillentine, L N Berry, R P Goin-Kochel, M A Ali, J Ge, D Guffey, J A Rosenfeld, V Hannig, P Bader, M Proud, M Shinawi, B H Graham, A Lin, S R Lalani, J Reynolds, M Chen, T Grebe, C G Minard, P Stankiewicz, A L Beaudet, C P Schaaf
Chromosome 15q11q13 is among the least stable regions in the genome due to its highly complex genomic architecture. Low copy repeat elements at 15q13.3 facilitate recurrent copy number variants (CNVs), with deletions established as pathogenic and CHRNA7 implicated as a candidate gene. However, the pathogenicity of duplications of CHRNA7 is unclear, as they are found in affected probands as well as in reportedly healthy parents and unaffected control individuals. We evaluated 18 children with microduplications involving CHRNA7, identified by clinical chromosome microarray analysis (CMA)...
March 2017: Journal of Autism and Developmental Disorders
https://www.readbyqxmd.com/read/27683195/first-evidence-of-smith-magenis-syndrome-in-mother-and-daughter-due-to-a-novel-rai-mutation
#12
Fabio Acquaviva, Maria Elena Sana, Matteo Della Monica, Michele Pinelli, Diana Postorivo, Paolo Fontana, Maria Teresa Falco, Anna Maria Nardone, Fortunato Lonardo, Maria Iascone, Gioacchino Scarano
Smith-Magenis syndrome (SMS) is a complex genetic disorder caused by interstitial 17p11.2 deletions encompassing multiple genes, including the retinoic acid induced 1 gene-RAI1-or mutations in RAI1 itself. The clinical spectrum includes developmental delay, cognitive impairment, and behavioral abnormalities, with distinctive physical features that become more evident with age. No patients have been reported to have had offspring. We here describe a girl with developmental delay, mainly compromising the speech area, and her mother with mild intellectual disabilities and minor dysmorphic features...
January 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/27648692/burn-injury-alters-epidermal-cholinergic-mediators-and-increases-hmgb1-and-caspase-3-in-autologous-donor-skin-and-burn-margin
#13
Casey J Holmes, Jennifer K Plichta, Richard L Gamelli, Katherine A Radek
Burn wound healing complications, such as graft failure or infection, are a major source of morbidity and mortality in burn patients. The mechanisms by which local burn injury alters epidermal barrier function in autologous donor skin and surrounding burn margin are largely undefined. We hypothesized that defects in the epidermal cholinergic system may impair epidermal barrier function and innate immune responses. The objective was to identify alterations in the epidermal cholinergic pathway, and their downstream targets, associated with inflammation and cell death...
February 2017: Shock
https://www.readbyqxmd.com/read/27610024/nicotinic-cholinergic-receptors-in-esophagus-early-alteration-during-carcinogenesis-and-prognostic-value
#14
Marina Chianello Nicolau, Luis Felipe Ribeiro Pinto, Pedro Nicolau-Neto, Paulo Roberto Alves de Pinho, Ana Rossini, Tatiana de Almeida Simão, Sheila Coelho Soares Lima
AIM: To compare expression of nicotinic cholinergic receptors (CHRNs) in healthy and squamous cell carcinoma-affected esophagus and determine the prognostic value. METHODS: We performed RT-qPCR to measure the expression of CHRNs in 44 esophageal samples from healthy individuals and in matched normal surrounding mucosa, and in tumors from 28 patients diagnosed with esophageal squamous cell carcinoma (ESCC). Next, we performed correlation analysis for the detected expression of these receptors with the habits and clinico-pathological characteristics of all study participants...
August 21, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27573666/role-of-the-%C3%AE-7-nicotinic-acetylcholine-receptor-and-ric-3-in-the-cholinergic-anti-inflammatory-pathway
#15
Millet Treinin, Roger L Papke, Eran Nizri, Yael Ben-David, Tehila Mizrachi, Talma Brenner
The nicotinic acetylcholine receptor (nAChR) gene family encodes for subunits of acetylcholine gated ion channels. These receptors are expressed widely and have many functions: They mediate excitation at neuro-muscular junctions. In the central nervous system nAChRs have been implicated in memory, cognition, and addiction. And in non-excitatory cells they regulate differentiation, proliferation and inflammatory responses. The CHRNA7 gene encodes for the a7 nAChR subunit that assembles into a homomeric receptor having unusual properties...
August 29, 2016: Central Nervous System Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/27565651/brief-report-initial-trial-of-alpha7-nicotinic-receptor-stimulation-in-two-adult-patients-with-autism-spectrum-disorder
#16
Ann Olincy, Audrey Blakeley-Smith, Lynn Johnson, William R Kem, Robert Freedman
Abnormalities in CHRNA7, the alpha7-nicotinic receptor gene, have been reported in autism spectrum disorder. These genetic abnormalities potentially decrease the receptor's expression and diminish its functional role. This double-blind, placebo-controlled crossover study in two adult patients investigated whether an investigational receptor-specific partial agonist drug would increase the inhibitory functions of the gene and thereby increase patients' attention. An electrophysiological biomarker, P50 inhibition, verified the intended neurobiological effect of the agonist, and neuropsychological testing verified a primary cognitive effect...
December 2016: Journal of Autism and Developmental Disorders
https://www.readbyqxmd.com/read/27459725/15q13-3-homozygous-knockout-mouse-model-display-epilepsy-autism-and-schizophrenia-related-phenotypes
#17
A Forsingdal, K Fejgin, V Nielsen, T Werge, J Nielsen
The 15q13.3 microdeletion syndrome is caused by a 1.5-MB hemizygous microdeletion located on 15q13.3 affecting seven genes: FAN1; MTMR10; TRPM1; miR-211; KLF13; OTUD7A; and CHRNA7. The 15q13.3 microdeletion increases the risk of intellectual disability, epilepsy, autism spectrum disorder and schizophrenia, though the clinical profile varies considerably. Two mouse models of this syndrome, with hemizygous deletion of the orthologous region in the murine genome, have recently been shown to recapitulate a number of the behavioral and physiological deficits that characterize the human condition...
2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27428758/nicotinic-cholinergic-and-dopaminergic-receptor-mrna-expression-in-male-and-female-rats-with-high-or-low-preference-for-nicotine
#18
Oguz Gozen, Tanseli Nesil, Lutfiye Kanit, Ersin O Koylu, Sakire Pogun
BACKGROUND: Nicotine exerts its central actions through nicotinic acetylcholine receptors (nAChRs), which in turn regulate major neurotransmitter systems including dopamine. Nicotinic and dopaminergic systems play significant roles in physiological functions, neuropsychiatric disorders, and addiction. OBJECTIVES: To evaluate possible differences in the expression of nAChR subunit and dopamine receptor (DR) mRNAs following voluntary nicotine intake. METHODS: Male and female rats (n = 67) were exposed to long-term free-choice oral nicotine (24 hours/day, 6 weeks); rats with maximum and minimum nicotine preference/intake were selected...
July 18, 2016: American Journal of Drug and Alcohol Abuse
https://www.readbyqxmd.com/read/27416040/molecular-signaling-and-dysfunction-of-the-human-reactive-enteric-glial-cell-phenotype-implications-for-gi-infection-ibd-poi-neurological-motility-and-gi-disorders
#19
Andromeda Liñán-Rico, Fabio Turco, Fernando Ochoa-Cortes, Alan Harzman, Bradley J Needleman, Razvan Arsenescu, Mahmoud Abdel-Rasoul, Paolo Fadda, Iveta Grants, Emmett Whitaker, Rosario Cuomo, Fievos L Christofi
BACKGROUND: Clinical observations or animal studies implicate enteric glial cells in motility disorders, irritable bowel syndrome, inflammatory bowel disease, gastrointestinal (GI) infections, postoperative ileus, and slow transit constipation. Mechanisms underlying glial responses to inflammation in human GI tract are not understood. Our goal was to identify the "reactive human enteric glial cell (rhEGC) phenotype" induced by inflammation, and probe its functional relevance. METHODS: Human enteric glial cells in culture from 15 GI-surgical specimens were used to study gene expression, Ca, and purinergic signaling by Ca/fluo-4 imaging and mechanosensitivity...
August 2016: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/27355804/snps-in-nrxn1-and-chrna5-are-associated-to-smoking-and-regulation-of-gabaergic-and-glutamatergic-pathways
#20
Gloria Pérez-Rubio, Martha E Pérez-Rodríguez, Juan Carlos Fernández-López, Alejandra Ramírez-Venegas, Jesús García-Colunga, Federico Ávila-Moreno, Angel Camarena, Raúl H Sansores, Ramcés Falfán-Valencia
AIM: To identify genetic variants associated with greater tobacco consumption in a Mexican population. PATIENTS & METHODS: Daily smokers were classified as light smokers (LS, n = 742), heavy smokers (HS; n = 601) and nonsmokers (NS, n = 606). In the first stage, a genotyping microarray that included 347 SNPs in CHRNA2-CHRNA7/CHRNA10, CHRNB2-CHRNB4 and NRXN1 genes and 37 ancestry-informative markers was used to analyze 707 samples (187 HS, 328 LS and 192 NS). In the second stage, 14 SNPs from stage 1 were validated in the remaining samples (HS, LS and NS; n = 414 in each group) using real-time PCR...
June 29, 2016: Pharmacogenomics
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