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https://www.readbyqxmd.com/read/29784875/a-human-specific-truncated-%C3%AE-7-nicotinic-receptor-subunit-assembles-with-full-length-%C3%AE-7-and-forms-functional-receptors-with-different-stoichiometries
#1
Matías Lasala, Jeremías Corradi, Ariana Bruzzone, María Del Carmen Esandi, Cecilia Bouzat
The cholinergic α7 nicotinic receptor gene, CHRNA7, encodes a subunit that forms the homopentameric α7 receptor, involved in learning and memory. In humans, exons 5-10 in CHRNA7 are duplicated and fused to the FAM7A genetic element, giving rise to the hybrid gene CHRFAM7A. Its product, dupα7, is a truncated subunit lacking part of the N-terminal extracellular ligand-binding domain and is associated with neurological disorders, including schizophrenia, and immunomodulation.We combined dupα7 expression on mammalian cells with patch clamp recordings to understand its functional role...
May 21, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29666375/association-and-cis-mqtl-analysis-of-variants-in-chrna3-a5-chrna7-chrnb2-and-chrnb4-in-relation-to-nicotine-dependence-in-a-chinese-han-population
#2
Qiang Liu, Haijun Han, Maiqiu Wang, Yinghao Yao, Li Wen, Keran Jiang, Yunlong Ma, Rongli Fan, Jiali Chen, Kunkai Su, Zhongli Yang, Wenyan Cui, Wenji Yuan, Xianzhong Jiang, Jingjing Li, Thomas J Payne, Jundong Wang, Ming D Li
Nicotine dependence (ND) is a worldwide health problem. Numerous genetic studies have demonstrated a significant association of variants in nicotinic acetylcholine receptors (nAChRs) with smoking behaviors. However, most of these studies enrolled only subjects of European or African ancestry. In addition, although an increasing body of evidence implies a causal connection of single-nucleotide polymorphisms (SNPs) and epigenetic regulation of gene expression, few studies of this issue have been reported. In this study, we performed both association and interaction analysis for 67 SNPs in CHRNA3-A5, CHRNA7, CHRNB2, and CHRNB4 with ND in a Chinese Han population (N = 5055)...
April 18, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29545933/endogenous-chrna7-ligand-slurp1-as-a-potential-tumor-suppressor-and-anti-nicotinic-factor-in-pancreatic-cancer
#3
Verena M Throm, David Männle, Thomas Giese, Andrea S Bauer, Matthias M Gaida, Juergen Kopitz, Thomas Bruckner, Konstanze Plaschke, Svetlana P Grekova, Klaus Felix, Thilo Hackert, Nathalia A Giese, Oliver Strobel
Smoking is associated with increased risk and poorer prognosis of pancreatic ductal adenocarcinoma (PDAC). Nicotine acts through cholinergic nicotinic receptors, preferentially α7 (CHRNA7) that also binds the endogenous ligand SLURP1 (Secreted Ly-6/uPAR-Related Protein 1). The clinical significance of SLURP1 and its interaction with nicotine in PDAC are unclear. We detected similar levels of SLURP1 in sera from healthy donors and patients with chronic pancreatitis or PDAC; higher preoperative values were associated with significantly better survival in patients with resected tumors...
February 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29305655/chrfam7a-gene-expression-in-schizophrenia-clinical-correlates-and-the-effect-of-antipsychotic-treatment
#4
Sunil V Kalmady, Rimjhim Agrawal, Deepthi Venugopal, Venkataram Shivakumar, Anekal C Amaresha, Sri Mahavir Agarwal, Manjula Subbanna, Ashwini Rajasekaran, Janardhanan C Narayanaswamy, Monojit Debnath, Ganesan Venkatasubramanian
Earlier studies have implicated CHRNA7, coding α-7 nicotinic acetylcholine receptor (α7 nAChR), and its partially duplicated chimeric gene CHRFAM7A in schizophrenia. However, the relationship between the alterations in peripheral gene expression of CHRFAM7A and severity of clinical symptoms has not been examined. Furthermore, potential influence of the antipsychotic medication on CHRFAM7A expression in drug-naive or drug-free schizophrenia is an unexplored area. CHRFAM7A gene expression in lymphocytes was analyzed in 90 antipsychotic-naïve or free schizophrenia patients using TaqMan-based quantitative RT-PCR...
April 2018: Journal of Neural Transmission
https://www.readbyqxmd.com/read/29304416/developmental-neurotoxicity-of-microcystis-aeruginosa-in-the-early-life-stages-of-zebrafish
#5
Haifeng Qian, Guangfu Liu, Tao Lu, Liwei Sun
Accumulating evidence suggests that cyanotoxins can exert neurotoxic effects on exposed aquatic organisms but most studies have focused on purified toxins rather than on the more complex effects of cyanobacterial blooms. To evaluate this issue in an environmentally relevant model, we assessed the developmental neurotoxicity induced by Microcystis aeruginosa on newly hatched zebrafish. After four days of exposure, the locomotor activity of zebrafish larvae was significantly decreased with increasing algae concentration...
April 30, 2018: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/29164477/genetic-variants-within-molecular-targets-of-antipsychotic-treatment-effects-on-treatment-response-schizophrenia-risk-and-psychopathological-features
#6
Marco Calabrò, Stefano Porcelli, Concetta Crisafulli, Sheng-Min Wang, Soo-Jung Lee, Changsu Han, Ashwin A Patkar, Prakash S Masand, Diego Albani, Ilaria Raimondi, Gianluigi Forloni, Sofia Bin, Carlotta Cristalli, Vilma Mantovani, Chi-Un Pae, Alessandro Serretti
Schizophrenia (SCZ) is a common and severe mental disorder. Genetic factors likely play a role in its pathophysiology as well as in treatment response. In the present study, we investigated the effects of several single nucleotide polymorphisms (SNPs) within 9 genes involved with antipsychotic (AP) mechanisms of action. Two independent samples were recruited. The Korean sample included 176 subjects diagnosed with SCZ and 326 healthy controls, while the Italian sample included 83 subjects and 194 controls. AP response as measured by the positive and negative syndrome scale (PANSS) was the primary outcome, while the secondary outcome was the SCZ risk...
January 2018: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29129316/functional-consequences-of-chrna7-copy-number-alterations-in-induced-pluripotent-stem-cells-and-neural-progenitor-cells
#7
Madelyn A Gillentine, Jiani Yin, Aleksandar Bajic, Ping Zhang, Steven Cummock, Jean J Kim, Christian P Schaaf
Copy-number variants (CNVs) of chromosome 15q13.3 manifest clinically as neuropsychiatric disorders with variable expressivity. CHRNA7, encoding for the α7 nicotinic acetylcholine receptor (nAChR), has been suggested as a candidate gene for the phenotypes observed. Here, we used induced pluripotent stem cells (iPSCs) and neural progenitor cells (NPCs) derived from individuals with heterozygous 15q13.3 deletions and heterozygous 15q13.3 duplications to investigate the CHRNA7-dependent molecular consequences of the respective CNVs...
December 7, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29114104/bidirectional-regulation-of-aggression-in-mice-by-hippocampal-alpha-7-nicotinic-acetylcholine-receptors
#8
Alan S Lewis, Steven T Pittenger, Yann S Mineur, Dawson Stout, Philip H Smith, Marina R Picciotto
Humans with 15q13.3 microdeletion syndrome (15q13.3DS) are typically hemizygous for CHRNA7, the gene coding for the α7 nicotinic acetylcholine receptor (nAChR), and manifest a variable neuropsychiatric phenotype that frequently includes persistent aggression. In mice, nAChR activation by nicotine is anti-aggressive, or 'serenic,' an effect which requires α7 nAChRs and is recapitulated by GTS-21, an α7 nAChR partial agonist. Pharmacotherapies potentiating α7 nAChR signaling have also been shown to reduce aggression in human 15q13...
November 7, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28978081/expression-patterns-for-nicotinic-acetylcholine-receptor-subunit-genes-in-smoking-related-lung-cancers
#9
Anna Bordas, José Luis Cedillo, Francisco Arnalich, Isabel Esteban-Rodriguez, Laura Guerra-Pastrián, Javier de Castro, Carolina Martín-Sánchez, Gema Atienza, Carmen Fernández-Capitan, Juan José Rios, Carmen Montiel
Cigarette smoking is associated with increased risk for all histologic types of lung cancer, but why the strength of this association is stronger for squamous cell carcinoma than adenocarcinoma of the lung (SQC-L, ADC-L) is not fully understood. Because nicotine and tobacco-specific nitrosamines contribute to carcinogenesis by activating nicotinic acetylcholine receptors (nAChRs) on lung tumors and epithelial cells, we investigated whether differential expression of nAChR subtypes in these tumors could explain their different association with smoking...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28890319/arctic-a%C3%AE-40-blocks-the-nicotine-induced-neuroprotective-effect-of-chrna7-by-inhibiting-the-erk1-2-pathway-in-human-neuroblastoma-cells
#10
Ye Ju, Toru Asahi, Naoya Sawamura
Amyloid β protein (Aβ) plays a central role in Alzheimer's disease (AD) pathogenesis. Point mutations in the Aβ sequence, which cluster around the central hydrophobic core of the peptide, are associated with familial AD (FAD). Several mutations have been identified, with the Arctic mutation exhibiting a purely cognitive phenotype that is typical of AD. Our previous findings suggest that Arctic Aβ40 binds to and aggregates with CHRNA7, thereby inhibiting the calcium response and signaling pathways downstream of the receptor...
September 8, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28867899/homology-modeling-and-protein-interaction-map-of-chrna7-neurogenesis-protein
#11
Ruchi Yadav, Deepshikha Deepshikha, Prachi Srivastava
CHRNA7 is a neurodevelopmental protein involved in differentiation and neurogenesis, which is also named as nicotinic acetylcholine receptors, cholinergic receptor, nicotinic, alpha 7 (neuronal). The protein encoded by this gene forms a homo-oligomeric channel. It is a major component of brain nicotinic receptors displays that are blocked by and sensitive to alpha-bungarotoxin. Studies reports involvement of CHRNA7 protein in different neurological diseases. Non-availability of 3-dimensional (3D) structure leads the study toward structure 3D prediction along with its interaction analysis...
July 2017: Annals of Neurosciences
https://www.readbyqxmd.com/read/28817303/chrna7-deletions-are-enriched-in-risperidone-treated-children-and-adolescents
#12
Madelyn A Gillentine, Janson J White, Christopher M Grochowski, James R Lupski, Christian P Schaaf, Chadi A Calarge
OBJECTIVE: Aggression is among the most common indications for referral to child and adolescent mental health services and is often challenging to treat. Understanding the biological underpinnings of aggression could help optimize treatment efficacy. Neuronal nicotinic acetylcholine receptors (nAChRs), specifically the α7 nAChR, encoded by the gene CHRNA7, have been implicated in aggressive behaviors in animal models as well as humans. Copy number variants (CNVs) of CHRNA7 are found in individuals with neuropsychiatric disorders, often with comorbid aggression...
August 17, 2017: Journal of Child and Adolescent Psychopharmacology
https://www.readbyqxmd.com/read/28791958/the-%C3%AE-7-nach-nicotinic-receptor-and-its-role-in-memory-and-selected-diseases-of-the-central-nervous-system
#13
REVIEW
Urszula Baranowska, Róża Julia Wiśniewska
α7-nACh is one of the major nicotinic cholinergic receptor subtypes found in the brain. It is broadly expressed in the hippocampal and cortical neurons, the regions which play a key role in memory formation. Although α7-nACh receptors may serve as postsynaptic receptors mediating classical neurotransmission, they usually function as presynaptic modulators responsible for the release of other neurotransmitters, such as glutamate, γ-aminobutyric acid, dopamine, and norepinephrine. They can, therefore, affect a wide array of neurobiological functions...
July 30, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28781257/-possible-involvement-of-neuronal-nicotinic-acetylcholine-receptors-in-compensatory-brain-mechanisms-at-early-stages-of-parkinson-s-disease
#14
E V Kryukova, I V Shelukhina, A A Kolacheva, A Kh Alieva, M I Shadrina, P A Slominsky, I E Kasheverov, Y N Utkin, M V Ugrumov, V I Tsetlin
A role of nicotinic acetylcholine receptors (nAChR) in the development of Parkinson's disease (PD) has been investigated using two mouse models corresponding to the presymptomatic stage and the early symptomatic stage of PD. Quantitative determination of nAChR in the striatum and substantia nigra (SN) was performed using the radioactive derivatives of epibatidine, -conotoxin MII, and -bungarotoxin as ligands. The number of ligand-binding sites changed differently depending on their location in the brain, the stage of the disease and the receptor subtype...
May 2017: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
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
#15
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...
October 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28699914/expression-patterns-for-nicotinic-acetylcholine-receptor-subunit-genes-in-smoking-related-lung-cancers
#16
Anna Bordas, José Luis Cedillo, Francisco Arnalich, Isabel Esteban-Rodriguez, Laura Guerra-Pastrián, Javier de Castro, Carolina Martín-Sánchez, Gema Atienza, Carmen Fernández-Capitan, Juan José Rios, Carmen Montiel
Cigarette smoking is associated with increased risk for all histologic types of lung cancer, but why the strength of this association is stronger for squamous cell carcinoma than adenocarcinoma of the lung (SQC-L, ADC-L) is not fully understood. Because nicotine and tobacco-specific nitrosamines contribute to carcinogenesis by activating nicotinic acetylcholine receptors (nAChRs) on lung tumors and epithelial cells, we investigated whether differential expression of nAChR subtypes in these tumors could explain their different association with smoking...
July 4, 2017: Oncotarget
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
#17
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
#18
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
#19
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
#20
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
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