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Jonathan B Rothbard, Jesse J Rothbard, Luis Soares, C Garrison Fathman, Lawrence Steinman
Although certain dogma portrays amyloid fibrils as drivers of neurodegenerative disease and neuroinflammation, we have found, paradoxically, that amyloid fibrils and small heat shock proteins (sHsps) are therapeutic in experimental autoimmune encephalomyelitis (EAE). They reduce clinical paralysis and induce immunosuppressive pathways, diminishing inflammation. A key question was the identification of the target for these molecules. When sHsps and amyloid fibrils were chemically cross-linked to immune cells, a limited number of proteins were precipitated, including the α7 nicotinic acetylcholine receptor (α7 NAChR)...
June 18, 2018: Proceedings of the National Academy of Sciences of the United States of America
Ginetta Collo, Laura Cavalleri, Michele Zoli, Uwe Maskos, Emiliangelo Ratti, Emilio Merlo Pich
Midbrain dopamine (DA) neurons are considered a critical substrate for the reinforcing and sensitizing effects of nicotine and tobacco dependence. While the role of the α4 and β2 subunit containing nicotinic acetylcholine receptors (α4β2∗ nAChRs) in mediating nicotine effects on DA release and DA neuron activity has been widely explored, less information is available on their role in the morphological adaptation of the DA system to nicotine, eventually leading to dysfunctional behaviors observed in nicotine dependence...
2018: Frontiers in Pharmacology
Svetlana Semenova, Xinchun Jin, Tristan D McClure-Begley, Matthew Philip Tadman, Michael J Marks, Athina Markou
BACKGROUND: Chronic nicotine exposure produces neuroadaptations in brain reward systems and α4β2 nicotinic acetylcholine receptors (nAChRs) in the corticolimbic brain areas. We previously demonstrated opposite effects of nicotine exposure delivered by self-administration or pumps on brain reward thresholds that can be attributed to the different temporal pattern and contingency of nicotine exposure. We investigated the effects of these two factors on reward thresholds and somatic signs during nicotine withdrawal, and on nAChRs binding in corticolimbic brain areas...
June 13, 2018: Pharmacology, Biochemistry, and Behavior
ArunSundar MohanaSundaram, Thukani Sathanantham Shanmugarajan, Velayutham Ravichandiran
Cognitive impulsivity, a form of suboptimal cost-benefit decision making is an illustrious attribute of an array of neurodegenerative diseases including Alzheimer's Disease (AD). In this study, delay discounting paradigm was used to assess the effect of 3,4-dihydroxyphenylethanol (DOPET) on cognitive impulsivity-in an oA42i (oligomeric amyloid β1-42 plus ibotenic acid) induced AD mouse model-using a non-spatial T-maze task. The results depicted that oA42i administration elevated cognitive impulsivity, whereas DOPET treatment attenuated the impulsive behavior and matched the choice of the sham-operated controls...
June 14, 2018: ACS Chemical Neuroscience
Nikita Abraham, Richard J Lewis
Marine cone snails are a large family of gastropods that have evolved highly potent venoms for predation and defense. The cone snail venom has exceptional molecular diversity in neuropharmacologically active compounds, targeting a range of receptors, ion channels, and transporters. These conotoxins have helped to dissect the structure and function of many of these therapeutically significant targets in the central and peripheral nervous systems, as well as unravelling the complex cellular mechanisms modulated by these receptors and ion channels...
June 13, 2018: Marine Drugs
Yao-Guo Han, Xiong Qin, Tao Zhang, Ming Lei, Fang-Yuan Sun, Jing-Jing Sun, Wei-Fang Yuan
Oxidative stress and neuroinflammation play an important role in the pathophysiology of lipopolysaccharide (LPS)-induced cognitive impairment. This study aims to observe the effect of electroacupuncture (EA) on the cognitive function in LPS-induced mice, and its regulation on hippocampal α7 nicotinic acetylcholine receptors (α7nAChR), oxidative and proinflammatory factors. Adult male C57BL/6 nice were used to establish animal model of LPS-induced cognitive impairment, and were randomly divided into three groups (n = 16): control group, model group (LPS: 5 mg/kg), and EA group...
June 6, 2018: Neuroscience Letters
Juan Camilo Jurado-Coronel, Alix E Loaiza, John E Díaz, Ricardo Cabezas, Ghulam Md Ashraf, Amirhossein Sahebkar, Valentina Echeverria, Janneth González, George E Barreto
Parkinson's disease (PD) is a neurodegenerative pathology characterized by resting tremor, rigidity, bradykinesia, and loss of dopamine-producing neurons in the pars compacta of the substantia nigra in the central nervous system (CNS) that result in dopamine depletion in the striatum. Oxidative stress has been documented as a key pathological mechanism for PD. Epidemiological studies have shown that smokers have a lower incidence of PD. In this aspect, different studies have shown that nicotine, a chemical compound found in cigarette, is capable of exerting beneficial effects in PD patients, but it can hardly be used as a therapeutic agent because of its inherent toxicity...
June 7, 2018: Molecular Neurobiology
Sue Wonnacott, Isabel Bermudez, Neil S Millar, Socrates J Tzartos
This themed section of the British Journal of Pharmacology is the product of a conference that focussed on nicotinic ACh receptors (nAChRs) that was held on the Greek island of Crete from 7 to 11 May 2017. 'Nicotinic acetylcholine receptors 2017' was the fourth in a series of triennial international meetings that have provided a regular forum for scientists working on all aspects of nAChRs to meet and to discuss new developments. In addition to many of the regular participants, each meeting has also attracted a new group of scientists working in a fast-moving area of research...
June 2018: British Journal of Pharmacology
Yixi Zhang, Xiaoyong Xu, Haibo Bao, Xusheng Shao, Zhong Li, Zewen Liu
BACKGROUND: Neonicotinoids, such as imidacloprid, are selective agonists of insect nicotinic acetylcholine receptors (nAChRs) to control Nilaparvata lugens, a major rice insect pest. High imidacloprid resistance has been reported in N. lugens in laboratory and in fields. Cycloxaprid, an oxabridged cis-nitromethylene neonicotinoid, showed high insecticidal activity against N. lugens and low cross-resistance in the imidacloprid resistant strains and field populations. RESULTS: Binding studies have demonstrated that imidacloprid had two binding sites with different affinities (Kd = 3...
June 6, 2018: Pest Management Science
A A Alahmari, B Sreekumar, V Patel, M Ashat, M Alexandre, A K Uduman, E O Akinbiyi, A Ceplenski, C A Shugrue, T R Kolodecik, N Tashkandi, S W Messenger, G E Groblewski, F S Gorelick, E C Thrower
Clinical studies have shown that cigarette smoking is a dose-dependent and independent risk factor for acute pancreatitis. Cigarette smoke contains nicotine which can be converted to the potent receptor ligand and toxin, NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone]. Previously, we have shown that NNK induces premature activation of pancreatic zymogens in rats, an initiating event in pancreatitis, and this activation is prevented by pharmacologic inhibition of nicotinic acetylcholine receptors (nAChR)...
2018: PloS One
S Lauren Kyte, David A Gewirtz
Studies in animal models have suggested that nicotine, an agonist of nicotinic acetylcholine receptors (nAChRs), may have the potential to prevent and/or reverse the peripheral neuropathy induced by cancer chemotherapeutic drugs, such as paclitaxel and oxaliplatin. However, a large body of evidence suggests that nicotine may also stimulate lung tumor growth and/or interfere with the effectiveness of cancer chemotherapy. While the reported proliferative effects of nicotine are highly variable, the antagonism of antitumor drug efficacy is more consistent, although this latter effect has been demonstrated primarily in cell culture studies...
June 4, 2018: Journal of Pharmacology and Experimental Therapeutics
Janyerson Dannys Pereira da Silva, Diego Vannucci Campos, Fabiana Moreira Nogueira-Bechara, Roberta Sessa Stilhano, Sang Won Han, Rita Sinigaglia-Coimbra, Maria Teresa R Lima-Landman, Antônio José Lapa, Caden Souccar
Dystrophin deficiency caused by mutations of the related gene leads to muscle wasting in Duchenne muscular dystrophy (DMD). Some patients with DMD also present with intellectual disability and various degrees of neurological disorders, which have been related to a decreased number of postsynaptic gamma-aminobutyric acid type A receptors (GABAA Rs) in the hippocampus (HPC) and cerebellum (CBL). The aim of this study was to examine the relevance of dystrophin in the presynaptic GABAergic function in brain regions in which this protein is normally abundant...
June 1, 2018: Neurochemistry International
Deniz Bagdas, Yasmin Alkhlaif, Asti Jackson, F Ivy Carroll, Joseph W Ditre, M Imad Damaj
Varenicline, a partial agonist for α4β2* nicotinic acetylcholine receptors (nAChRs) and a full agonist for α3β4 and α7 nAChRs, is approved for smoking cessation treatment. Although, partial agonism at α4β2* nAChRs is believed to be the mechanism underlying the effects of varenicline on nicotine reward, the contribution of other nicotinic subtypes to varenicline's effects on nicotine reward is currently unknown. Therefore, we examined the role of α5 and α7 nAChR subunits in the effects of varenicline on nicotine reward using the conditioned place preference (CPP) test in mice...
May 21, 2018: Neuropharmacology
Chelsea T Tiernan, Stephen D Ginsberg, Bin He, Sarah M Ward, Angela L Guillozet-Bongaarts, Nicholas M Kanaan, Elliott J Mufson, Scott E Counts
Cholinergic basal forebrain neurons of the nucleus basalis of Meynert (nbM) regulate attentional and memory function and are exquisitely prone to tau pathology and neurofibrillary tangle (NFT) formation during the progression of Alzheimer's disease (AD). nbM neurons require the neurotrophin nerve growth factor (NGF), its cognate receptor TrkA, and the pan-neurotrophin receptor p75NTR for their maintenance and survival. Additionally, nbM neuronal activity and cholinergic tone are regulated by the expression of nicotinic (nAChR) and muscarinic (mAChR) acetylcholine receptors as well as receptors modulating glutamatergic and catecholaminergic afferent signaling...
May 31, 2018: Neurobiology of Disease
Satoshi Muneoka, Ryuichi Nakamura, Masato Hoshino, Kimiaki Utsugisawa, Tomohiro Makino
Membrane proteins, such as G-protein-coupled receptors and ion channels are attractive targets for antibody-based therapeutics as pharmaceutical and biotech companies have increasingly moved their attention to biologics. However, lack of appropriate screening systems to correctly detect specific antibodies against membrane proteins has hampered antibody discovery and development so far. In the present study, we described the development of a novel high-throughput immunoassay platform based on AlphaLISA to screen antibodies against intact membrane proteins, taking nicotinic acetylcholine receptor (nAChR), one of the best-known ion channel membrane proteins, as an example...
May 29, 2018: Journal of Bioscience and Bioengineering
Julien Giribaldi, David Wilson, Annette Nicke, Yamina El Hamdaoui, Guillaume Laconde, Adèle Faucherre, Hamid Moha Ou Maati, Norelle L Daly, Christine Enjalbal, Sébastien Dutertre
Cone snails produce a fast-acting and often paralyzing venom that is usually injected into their prey or predator through a hypodermic needle-like modified radula tooth. Many diverse compounds are found in their venom including small molecules, peptides and enzymes. However, peptidic toxins called conotoxins (10⁻40 residues and 2⁻4 disulfide bonds) largely dominate these cocktails. These disulfide rich toxins are very valuable pharmacological tools for investigating the function of ions channels, G-protein coupled receptors, transporters and enzymes...
June 1, 2018: Toxins
Lila Buls Wollman, Richard B Levine, Ralph F Fregosi
We tested the hypothesis that nicotine exposure in utero and after birth (developmental nicotine exposure, DNE), disrupts development of glycinergic synaptic transmission to hypoglossal motoneurons (XIIMNs). Glycinergic spontaneous and miniature inhibitory postsynaptic currents (sIPSC/mIPSC) were recorded from XIIMNs in brainstem slices from 1-5-day old rat pups of either sex, under baseline conditions and following stimulation of nicotinic acetylcholine receptors (nAChRs) with nicotine (i.e., an acute nicotine challenge)...
May 30, 2018: Journal of Neurophysiology
Yuan-Hao Chen, Bon-Jour Lin, Tsung-Hsun Hsieh, Tung-Tai Kuo, Jonathan Miller, Yu-Ching Chou, Eagle Yi-Kung Huang, Barry J Hoffer
BACKGROUND: The aim of this work was to determine the effect of nicotine desensitization on dopamine (DA) release in the dorsal striatum and shell of the nucleus accumbens (NAc) from brain slices. MATERIALS AND METHODS: In vitro fast-scan cyclic voltammetry analysis was used to evaluate dopamine release in the dorsal striatum and the NAc shell of Sprague-Dawley rats after infusion of nicotine, a nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine (Mec), and an α4β2 cholinergic receptor antagonist (DHβe)...
January 1, 2018: Cell Transplantation
Sami Alzarea, Shafiqur Rahman
Evidence suggests that α7 nicotinic acetylcholine receptor (α7 nAChR) in the central nervous system has a critical role in the regulation of microglial function and neuroinflammation associated with the pathophysiology of major depressive disorder (MDD). The objectives of the present study were to determine the effects of PNU 120596, an α7 nAChR positive allosteric modulator (PAM), on depressive-like behavior and expression of ionized calcium binding adaptor molecule 1 (Iba-1), a microglial marker, in male C57BL/6J mice following lipopolysaccharide (LPS) administration, an animal model for depressive-like behavior...
May 22, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
De-Jie Chen, Fen-Fei Gao, Xiao-Kuang Ma, Gang-Gang Shi, Yuan-Bing Huang, Quang-Xi Su, Sterling Sudweeks, Ming Gao, Turner Dharshaun, Jason Brek Eaton, Yong-Chang Chang, J Michael Mcintosh, Ronald J Lukas, Paul Whiteaker, Scott C Steffensen, Jie Wu
Neuronal nicotinic acetylcholine receptors containing α6 subunits (α6* -nAChRs) show highly restricted distribution in midbrain neurons associated with pleasure, reward, and mood control, suggesting an important impact of α6* -nAChRs in modulating mesolimbic functions. However, the function and pharmacology of α6* -nAChRs remain poorly understood because of the lack of selective agonists for α6* -nAChRs and the challenging heterologous expression of functional α6* -nAChRs in mammalian cell lines. In particular, the α6 subunit is commonly co-expressed with α4* -nAChRs in the midbrain, which masks α6* -nAChR (without α4) function and pharmacology...
May 24, 2018: Acta Pharmacologica Sinica
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