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Candace Jones
PURPOSE: The aim of this article is to review the recent trials of α7 nicotinic acetylcholine receptor (α7 nAChR) agonists and positive allosteric modulators (PAMs) on the treatment of cognitive decline in schizophrenia. α7 Nicotinic acetylcholine receptor abnormalities in schizophrenia and clinical implications of α7 nAChR agonists and PAMs are also discussed. PROCEDURES: Studies were searched on PubMed with keywords "nicotinic," "alpha7," and "schizophrenia" over a 2-year period: January 1, 2016, to December 1, 2017...
March 2, 2018: Journal of Clinical Psychopharmacology
Liping Yang, Rong Wang, Shixing Yang, Zexu Ma, Shaoli Lin, Yuchen Nan, Qisheng Li, Qiyi Tang, Yan-Jin Zhang
Movement of macromolecules between the cytoplasm and the nucleus occurs through the nuclear pore complex (NPC). Karyopherins comprise a family of soluble transport factors facilitating nucleocytoplasmic translocation of proteins through the NPC. In this study, we discovered that karyopherin alpha6 (KPNA6, also known as importin alpha7) was required for the optimal replication of porcine reproductive and respiratory syndrome virus (PRRSV) and Zika virus (ZIKV), which are positive-sense, single-stranded RNA viruses replicating in the cytoplasm...
February 14, 2018: Journal of Virology
Dong Mei, Libo Zhao, Binlong Chen, Xiaoyan Zhang, Xiaoling Wang, Zhiying Yu, Xin Ni, Qiang Zhang
A micelle system modified with α-Conotoxin ImI (ImI), a potently antagonist for alpha7 nicotinic acetylcholine receptor (α7-nAChR) previously utilized for targeting breast cancer, was constructed. Its targeting efficiency and cytotoxicity against non-small cell lung cancer (NSCLC) highly expressing α7-nAChR was investigated. A549, a non-small cell lung cancer cell line, was selected as the cell model. The cellular uptake study showed that the optimal modification ratio of ImI on micelle surface was 5% and ImI-modification increased intracellular delivery efficiency to A549 cells via receptor-mediated endocytosis...
November 2018: Drug Delivery
Coral M Capó-Vélez, Bryan Morales-Vargas, Aurian García-González, José G Grajales-Reyes, Manuel Delgado-Vélez, Bismark Madera, Carlos A Báez-Pagán, Orestes Quesada, José A Lasalde-Dominicci
Currently, there are no specific therapies to treat HIV-1 associated neurocognitive disorders (HAND). The HIV-1 envelope, gp120, induces neuropathological changes similar to those in HAND patients; furthermore, it triggers an upregulation of the α7-nicotinic acetylcholine receptor (α7-nAChR), facilitating intracellular calcium overload and neuronal cell death. Using a gp120IIIB-transgenic mouse (gp120-tgm) model, we demonstrate that α7-nAChRs are upregulated on striatal neurons. Activation of α7-nAChRs leads to an increase in both intracellular calcium and percentage of apoptotic cells, which can be abrogated by antagonizing the receptor, suggesting a role for α7-nAChRs in gp120-induced neurotoxicity...
January 29, 2018: Scientific Reports
A E Gaydukov, O P Balezina
We investigated the involvement of calcium-dependent enzymes, protein kinase C (PKC) and calcium-calmodulin-dependent protein kinase II (CaMKII), in the signaling pathway triggered by the activation of presynaptic alpha7-type nicotinic acetylcholine receptors by exogenous choline, leading to downregulation of the evoked acetylcholine (ACh) release in mouse motor synapses. Blockade of PKC with chelerythrine neither changed the evoked release of ACh by itself nor prevented the inhibitory effect of choline. The CaMKII blocker KN-62 did not affect synaptic activity but fully prevented the choline-induced downregulation of ACh release...
October 2017: Acta Naturae
Mohammad Seyedabadi, Reza Rahimian, Jean-Eric Ghia
Autonomic imbalance plays a pivotal role in the pathophysiology of inflammatory bowel diseases (IBD). The central nervous system (CNS) cooperates dynamically with the immune system to regulate inflammation through humoral and neural pathways. In particular, acetylcholine (Ach), the main neurotransmitter in the vagus nerve, decreases the production of pro-inflammatory cytokines through a mechanism dependent on the α7 nicotinic Ach receptors (α7nAChRs). Areas covered: Here, we review the evidence for involvement of the cholinergic anti-inflammatory pathway (CAP) in IBD...
February 2018: Expert Opinion on Therapeutic Targets
Xin-Xin Lu, Zhong-Qiu Hong, Zhi Tan, Ming-Hong Sui, Zhi-Qiang Zhuang, Hui-Hua Liu, Xiu-Yuan Zheng, Tie-Bin Yan, Deng-Feng Geng, Dong-Mei Jin
BACKGROUND The role of nicotinic acetylcholine receptor alpha7 subunit (a7nAchR) in the treatment of acute cerebral ischemia by VNS has not been thoroughly clarified to date. Therefore, this study aimed to investigate the specific role of a7nAchR and explore whether this process is involved in the mechanisms of VNS-induced neuroprotection in rats undergoing permanent middle cerebral artery occlusion (PMCAO) surgery. MATERIAL AND METHODS Rats received a7nAChR antagonist (A) or antagonist placebo injection for control (AC), followed by PMCAO and VNS treatment, whereas the a7nAChR agonist (P) was utilized singly without VNS treatment but only with PMCAO pretreatment...
December 23, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Dan Zhao, Xulin Xu, Linna Pan, Wei Zhu, Xiaopei Fu, Lianjun Guo, Qing Lu, Jian Wang
BACKGROUND: It has been shown that chronic stress-induced depression is associated with exaggerated inflammatory response in the brain. Alpha7 nicotinic acetylcholine receptors (α7nAChRs) regulate the cholinergic anti-inflammatory pathway, but the role of cholinergic signaling and α7nAChR in chronic stress has not yet been examined. METHODS: In this study, we used a well-documented model of depression in which mice were exposed to 6 h of restraint stress for 21 consecutive days...
December 2, 2017: Journal of Neuroinflammation
Kazuyuki Takata, Takahide Amamiya, Hiroaki Mizoguchi, Shohei Kawanishi, Eriko Kuroda, Risa Kitamura, Aina Ito, Yuki Saito, Manami Tawa, Tomofumi Nagasawa, Haruka Okamoto, Yuko Sugino, Shigehiko Takegami, Tatsuya Kitade, Yuki Toda, William R Kem, Yoshihisa Kitamura, Shun Shimohama, Eishi Ashihara
We previously demonstrated that stimulation of nicotinic acetylcholine receptors (nAChRs) increases amyloid-β (Aβ) phagocytosis in rat microglia and is closely associated with the decrease of brain Aβ and amelioration of memory dysfunction in a transgenic mouse model of Alzheimer's disease (AD). Here, we examined the subtypes of nAChRs involved in these beneficial effects. In primary cultures of rat microglia, the α7 nAChR selective agonist 3-[(2,4-dimethoxy)benzylidene]-anabaseine dihydrochloride (DMXBA) promoted Aβ and fluorescent latex bead phagocytosis, whereas selective α7 nAChR antagonists suppressed the enhanced Aβ phagocytosis...
February 2018: Neurobiology of Aging
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...
January 15, 2018: Neuroscience
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
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
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
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
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
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
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
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
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
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
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