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https://www.readbyqxmd.com/read/29126954/quantitative-analysis-of-kynurenine-aminotransferase-ii-in-the-adult-rat-brain-reveals-high-expression-in-proliferative-zones-and-corpus-callosum
#1
Chang Song, Sarah M Clark, Chloe N Vaughn, James D Nicholson, Kelley J Murphy, Ta-Chung M Mou, Robert Schwarcz, Gloria E Hoffman, Leonardo H Tonelli
Kynurenic acid, a metabolite of the kynurenine pathway of tryptophan degradation, acts as an endogenous antagonist of alpha7 nicotinic and NMDA receptors and is implicated in a number of neurophysiological and neuropathological processes including cognition and neurodegenerative events. Therefore, kynurenine aminotransferase II (KAT II/AADAT), the enzyme responsible for the formation of the majority of neuroactive kynurenic acid in the brain, has prompted significant interest. Using immunohistochemistry, this enzyme was localized primarily in astrocytes throughout the adult rat brain, but detailed neuroanatomical studies are lacking...
November 8, 2017: Neuroscience
https://www.readbyqxmd.com/read/29117258/lung-epithelial-response-to-cigarette-smoke-and-modulation-by-the-nicotinic-alpha-7-receptor
#2
Lorise C Gahring, Elizabeth J Myers, Diane M Dunn, Robert B Weiss, Scott W Rogers
Cigarette smoking (CS) is a principal contributor to a spectrum of devastating lung diseases whose occurrence and severity may vary between individuals and not appear for decades after prolonged use. One explanation for the variability and delay in disease onset is that nicotine, the addictive component of CS, acts through the ionotropic nicotinic acetylcholine receptor (nAChR) alpha7 (α7) to modulate anti-inflammatory protection. In this study we measured the impact α7 signaling has on the mouse distal lung response to side-stream CS exposure for mice of the control genotype (α7G) and those in which the α7-receptor signaling mechanisms are restricted by point mutation (α7E260A:G)...
2017: PloS One
https://www.readbyqxmd.com/read/28993233/the-distribution-of-the-alpha7-nicotinic-acetylcholine-receptor-in-healthy-aging-an-in-vivo-positron-emission-tomography-study-with-18-f-asem
#3
Jennifer M Coughlin, Yong Du, Hailey B Rosenthal, Stephanie Slania, Soo Min Koo, Andrew Park, Ghedem Solomon, Melin Vranesic, Inga Antonsdottir, Caroline L Speck, Kelly Rootes-Murdy, Alexandria Lerner, Steven P Rowe, Yuchuan Wang, Wojciech G Lesniak, Il Minn, Arnold Bakker, Gwenn S Smith, Robert F Dannals, Hiroto Kuwabara, Andrew Horti, Dean F Wong, Martin G Pomper
Altered function of the alpha7 nicotinic acetylcholine receptor (α7-nAChR) is implicated in several neuropsychiatric diseases. Nevertheless, studies of the human cerebral α7-nAChR even in healthy aging are limited in number and to postmortem tissue. METHODS: The distribution of the cerebral α7-nAChR was estimated in nine brain regions in 25 healthy volunteers (ages 21-86 years; median 57 years, interquartile range 52 years) using [(18)F]ASEM with positron emission tomography (PET) imaging...
October 7, 2017: NeuroImage
https://www.readbyqxmd.com/read/28955138/alpha7-nachr-agonists-for-cognitive-deficit-and-negative-symptoms-in-schizophrenia-a-meta-analysis-of-randomized-double-blind-controlled-trials
#4
Ye Jin, Qi Wang, Yan Wang, Mengxi Liu, Anji Sun, Zhongli Geng, Yiwei Lin, Xiaobai Li
BACKGROUND: Previous clinical trials of α7-nicotinic acetylcholine receptor agonists (α7-nAChR agonists) showed mixed results in treating the cognitive and negative symptoms of schizophrenia. AIMS: To assess the efficacy and safety of α7-nAChR agonists in treating the cognitive and negative symptoms in schizophrenia. METHODS: A literature search was conducted to identify randomized double-blind placebo-controlled trials for schizophrenia published before May 26, 2017, by searching PubMed, Embase, ClinicalTrials...
August 25, 2017: Shanghai Archives of Psychiatry
https://www.readbyqxmd.com/read/28928637/alpha7-nicotinic-acetylcholine-receptors-play-a-predominant-role-in-the-cholinergic-potentiation-of-n-methyl-d-aspartate-evoked-firing-responses-of-hippocampal-ca1-pyramidal-cells
#5
Zsolt K Bali, Lili V Nagy, István Hernádi
The aim of the present study was to identify in vivo electrophysiological correlates of the interaction between cholinergic and glutamatergic neurotransmission underlying memory. Extracellular spike recordings were performed in the hippocampal CA1 region of anesthetized rats in combination with local microiontophoretic administration of N-methyl-D-aspartate (NMDA) and acetylcholine (ACh). Both NMDA and ACh increased the firing rate of the neurons. Furthermore, the simultaneous delivery of NMDA and ACh resulted in a more pronounced excitatory effect that was superadditive over the sum of the two mono-treatment effects and that was explained by cholinergic potentiation of glutamatergic neurotransmission...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28836276/the-expression-localization-and-function-of-%C3%AE-7-nicotinic-acetylcholine-receptor-in-rat-corpus-cavernosum
#6
Hedyeh Faghir-Ghanesefat, Nastaran Rahimi, Fatemeh Yarmohammadi, Tahmineh Mokhtari, Ali Reza Abdollahi, Shahram Ejtemaei Mehr, Ahmad R Dehpour
OBJECTIVES: Alpha7 nicotinic acetylcholine receptor (α7-nAChR), an emerging pharmacological target for a variety of medical conditions, is expressed in the most mammalian tissues with different effects. So, this study was designed to investigate the expression, localization and effect of α7-nAChR in rat corpus cavernosum (CC). METHODS & KEY FINDINGS: Reverse transcription polymerase chain reaction (RT-PCR) revealed that α7-nAChR was expressed in rat CC and double immunofluorescence studies demonstrated the presence of α7-nAChR in corporal neurons...
August 24, 2017: Journal of Pharmacy and Pharmacology
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
#7
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/28763248/evaluating-commercially-available-antibodies-for-rat-%C3%AE-7-nicotinic-acetylcholine-receptors
#8
Brijesh K Garg, Ralph H Loring
Alpha7 nicotinic acetylcholine receptors (α7 nAChRs) are important drug targets in neurological disorders and inflammation, making their detection and localization by validated antibodies highly desirable. However, tests in knockout animals raised questions about specificity of antibodies to mouse α7 nAChRs. To date, methods for validating antibodies for rat or human α7 nAChR have not been reported. We developed a gel-shift assay for western blots using GH4C1 cells expressing either native rat receptors or α7 nAChR-green fluorescent protein (GFP) chimeras to evaluate seven commercially available α7 nAChR antibodies...
September 2017: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/28684359/significance-of-the-nicotinic-alpha7-receptor-in-cognition-and-antipsychotic-like-behavior-in-the-rat
#9
Marie-Louise G Wadenberg, Dina Manetti, Maria Novella Romanelli, Hugo R Arias
Schizophrenic (SCH) patients show cognitive impairment in attentional performance. Positive allosteric modulators (PAMs) of α7 nicotinic acetylcholine receptors (nAChRs) such as the Alzheimer's drug galantamine (GAL) and PAM-2 are documented to have pro-cognitive properties. However, it is not well established if these properties would be lost, or may hamper antipsychotic efficacy, when given as an adjunct to an antipsychotic which is needed for managing psychotic symptoms. Using adult male Wistar rats, we here investigated the effects of: a) GAL, alone or co-administered with the antipsychotic risperidone (RISP), on acute phencyclidine (PCP)-induced deficits in the attentional set-shifting (ASST) test; b) PAM-2, alone and co-administered with RISP, in the conditioned avoidance response (CAR) test for antipsychotic activity...
July 3, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28559895/autophagy-plays-an-important-role-in-anti-inflammatory-mechanisms-stimulated-by-alpha7-nicotinic-acetylcholine-receptor
#10
Bo-Zong Shao, Ping Ke, Zhe-Qi Xu, Wei Wei, Ming-He Cheng, Bin-Ze Han, Xiong-Wen Chen, Ding-Feng Su, Chong Liu
Alpha7 nicotinic acetylcholine receptor (α7nAChR) has been reported to alleviate neuroinflammation. Here, we aimed to determine the role of autophagy in α7nAChR-mediated inhibition of neuroinflammation and its underlying mechanism. Experimental autoimmune encephalomyelitis (EAE) mice and lipopolysaccharide-stimulated BV2 microglia were used as in vivo and in vitro models of neuroinflammation, respectively. The severity of EAE was evaluated with neurological scoring. Autophagy-related proteins (Beclin 1, LC3-II/I, p62/SQSTM1) were detected by immunoblot...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28547815/balancing-the-autonomic-nervous-system-to-reduce-inflammation-in-rheumatoid-arthritis
#11
REVIEW
F A Koopman, M A van Maanen, M J Vervoordeldonk, P P Tak
Imbalance in the autonomic nervous system (ANS) has been observed in many established chronic autoimmune diseases, including rheumatoid arthritis (RA), which is a prototypic immune-mediated inflammatory disease (IMID). We recently discovered that autonomic dysfunction precedes and predicts arthritis development in subjects at risk of developing seropositive RA. In addition, RA patients with relatively high vagus nerve tone (higher parasympathetic parameters, measured by heart rate variability) respond better to antirheumatic therapies...
July 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28506554/selective-dopamine-receptor-4-activation-mediates-the-hippocampal-neuronal-calcium-response-via-ip3-and-ryanodine-receptors
#12
Ya-Li Wang, Jian-Gang Wang, Fang-Li Guo, Xia-Huan Gao, Dan-Dan Zhao, Lin Zhang, Jian-Zhi Wang, Cheng-Biao Lu
Intracellular calcium is a key factor in most cellular processes, including cell growth, differentiation, proliferation and neurotransmitter release. Dopamine (DA) mediates synaptic transmission by regulating the intracellular calcium content. It is not clear, however, which specific subunit of the DA receptor contributes to DA modulation of intracellular calcium content changes. Through the traditional technique of Fura-2 calcium imaging, this study demonstrated that the DA can induce transient calcium in cultured hippocampal neurons and that this response can be mimicked by a selective dopamine receptor 4 (DR4) agonist PD168077 (PD)...
May 12, 2017: Brain Research
https://www.readbyqxmd.com/read/28496108/alpha7-nicotinic-acetylcholine-receptor-agonist-promotes-retinal-ganglion-cell-function-via-modulating-gabaergic-presynaptic-activity-in-a-chronic-glaucomatous-model
#13
Xujiao Zhou, Yun Cheng, Rong Zhang, Gang Li, Boqi Yang, Shenghai Zhang, Jihong Wu
Alpha-7 nicotinic acetylcholine receptor (α7-nAChR) agonists can prevent glutamate-induced excitotoxicity in cultured retinal ganglion cells (RGCs). However, the neuroprotective effects and the mechanism of action of PNU-282987, an α7-nAChR agonist, in a chronic in vivo rat glaucoma model are poorly understood. We found that elevated intraocular pressure (IOP) downregulated retinal α7-nAChR expression. Electroretinography revealed that the amplitude of the photopic negative response (PhNR) decreased in parallel with the loss of RGCs caused by elevated IOP...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28419874/oral-administration-of-a-specific-kynurenic-acid-synthesis-kat-ii-inhibitor-attenuates-evoked-glutamate-release-in-rat-prefrontal-cortex
#14
D M Bortz, H-Q Wu, R Schwarcz, J P Bruno
Cognitive deficits represent core symptoms in schizophrenia (SZ) and predict patient outcome; however, they remain poorly treated by current antipsychotic drugs. Elevated levels of the endogenous alpha7 nicotinic receptor negative allosteric modulator and NMDA receptor antagonist, kynurenic acid (KYNA), are commonly seen in post-mortem tissue and cerebrospinal fluid of patients with SZ. When acutely or chronically elevated in rodents, KYNA produces cognitive deficits similar to those seen in the disease, making down-regulation of KYNA, via inhibition of kynurenine aminotransferase II (KAT II), a potential treatment strategy...
July 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28384302/nicotinic-alpha-7-receptor-expression-and-modulation-of-the-lung-epithelial-response-to-lipopolysaccharide
#15
Lorise C Gahring, Elizabeth J Myers, Diane M Dunn, Robert B Weiss, Scott W Rogers
Nicotine modulates multiple inflammatory responses in the lung through the nicotinic acetylcholine receptor subtype alpha7 (α7). Previously we reported that α7 modulates both the hematopoietic and epithelium responses in the lung to the bacterial inflammogen, lipopolysaccharide (LPS). Here we apply immunohistochemistry, flow cytometry and RNA-Seq analysis of isolated distal lung epithelium to further define α7-expression and function in this tissue. Mouse lines were used that co-express a bicistronic tau-green fluorescent protein (tGFP) as a reporter of α7 (α7G) expression and that harbor an α7 with a specific point mutation (α7E260A:G) that selectively uncouples it from cell calcium-signaling mechanisms...
2017: PloS One
https://www.readbyqxmd.com/read/28282360/an-alpha7-nicotinic-acetylcholine-receptor-agonist-gts-21-promotes-c2c12-myonuclear-accretion-in-association-with-release-of-interleukin-6-il-6-and-improves-survival-in-burned-mice
#16
Mohammed A S Khan, Mohammed F Khan, Shizuka Kashiwagi, William R Kem, Shingo Yasuhara, Masao Kaneki, Ronald G Tompkins, Jeevendra A J Martyn
The role of interleukin-6 (IL-6) in physiological processes and disease is poorly understood. The hypothesis tested in this study was that selective alpha7 acetylcholine receptor (α7AChR) agonist, GTS-21, releases IL-6 in association with myonuclear accretion and enhances insulin signaling in muscle cells, and improves survival of burn injured (BI) mice. The in vitro effects of GTS-21 were determined in C2C12 myoblasts and 7-day differentiated myotubes (myotubes). The in vivo effects of GTS-21 were tested in BI wild-type (WT) and IL-6 knockout (IL6KO) mice...
August 2017: Shock
https://www.readbyqxmd.com/read/28243714/nicotine-withdrawal-induced-inattention-is-absent-in-alpha7-nachr-knockout-mice
#17
K K Higa, A Grim, M E Kamenski, J van Enkhuizen, X Zhou, K Li, J C Naviaux, L Wang, R K Naviaux, M A Geyer, A Markou, J W Young
RATIONALE: Smoking is the leading cause of preventable death in the USA, but quit attempts result in withdrawal-induced cognitive dysfunction and predicts relapse. Greater understanding of the neural mechanism(s) underlying these cognitive deficits is required to develop targeted treatments to aid quit attempts. OBJECTIVES: We examined nicotine withdrawal-induced inattention in mice lacking the α7 nicotinic acetylcholine receptor (nAChR) using the five-choice continuous performance test (5C-CPT)...
May 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28196430/first-in-human-trial-of-a-type-i-positive-allosteric-modulator-of-alpha7-nicotinic-acetylcholine-receptors-pharmacokinetics-safety-and-evidence-for-neurocognitive-effect-of-avl-3288
#18
Kelvin W Gee, Ann Olincy, Richard Kanner, Lynn Johnson, Derk Hogenkamp, Josette Harris, Minhtam Tran, Stephen A Edmonds, William Sauer, Ryan Yoshimura, Timothy Johnstone, Robert Freedman
Type I positive allosteric modulators (PAMs) of the alpha7-nicotinic receptor enhance its cholinergic activation while preserving the spatiotemporal features of synaptic transmission and the receptor's characteristic rapid desensitization kinetics. Alpha7-nicotinic receptor agonists have shown promise for improving cognition in schizophrenia, but longer-term trials have been disappointing. Therefore, the type I PAM AVL-3288 was evaluated for safety and preliminary evidence of neurocognitive effect in healthy human subjects...
February 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28168926/stimulation-of-nicotinic-acetylcholine-alpha7-receptors-rescue-schizophrenia-like-cognitive-impairments-in-rats
#19
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/28147247/evidence-of-brdu-positive-retinal-neurons-after-application-of-an-alpha7-nicotinic-acetylcholine-receptor-agonist
#20
Mark K Webster, Cynthia A Cooley-Themm, Joseph D Barnett, Harrison B Bach, Jessica M Vainner, Sarah E Webster, Cindy L Linn
Irreversible vision loss due to disease or age is responsible for a reduced quality of life. The experiments in this study test the hypothesis that the α7 nicotinic acetylcholine receptor agonist, PNU-282987, leads to the generation of retinal neurons in an adult mammalian retina in the absence of retinal injury or exogenous growth factors. Using antibodies against BrdU, retinal ganglion cells, progenitor cells and Müller glia, the results of this study demonstrate that multiple types of retinal cells and neurons are generated after eye drop application of PNU-282987 in adult Long Evans rats in a dose-dependent manner...
March 27, 2017: Neuroscience
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