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Neurotransmission

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https://www.readbyqxmd.com/read/28731329/generation-and-characterization-of-anti-vglut-nanobodies-acting-as-inhibitors-of-transport
#1
Stephan Schenck, Laura Kunz, Daniela Sahlender, Els Pardon, Eric R Geertsma, Iaroslav Savtchouk, Toshiharu Suzuki, Yvonne Neldner, Saša Štefanić, Jan Steyaert, Andrea Volterra, Raimund Dutzler
The uptake of glutamate by synaptic vesicles is mediated by vesicular glutamate transporters (VGLUTs). The central role of these transporters in excitatory neurotransmission underpins their importance as pharmacological targets. Although several compounds inhibit VGLUTs, highly specific inhibitors were so far unavailable, thus limiting applications to in vitro experiments. Besides their potential in pharmacology, specific inhibitors would also be beneficial for the elucidation of transport mechanisms. To overcome this shortage, we generated nanobodies (Nbs) by immunization of a llama with purified rat VGLUT1 and subsequent selection of binders from a phage display library...
July 21, 2017: Biochemistry
https://www.readbyqxmd.com/read/28730966/nicotinic-cholinergic-system-in-the-hypothalamus-modulates-the-activity-of-the-hypothalamic-neuropeptides-during-the-stress-resp
#2
Burcu Balkan, Sakire Pogun
The hypothalamus harbors high levels of cholinergic neurons and axon terminals. Nicotinic acetylcholine receptors, which play an important role in cholinergic neurotransmission, are expressed abundantly in the hypothalamus. Accumulating evidence reveals a regulatory role for nicotine in diverse functions mediated by the hypothalamus, including the regulation of the stress responses. The nicotinic cholinergic system lies at the intersection of homeostatic and reward pathways and shows sex differences in some of its effects...
July 19, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28730831/the-galanin-and-galanin-receptor-subtypes-its-regulatory-role-in-the-biological-and-pathological-functions
#3
J Šípková, I Kramáriková, S Hynie, V Klenerová
The multitalented neuropeptide galanin was first discovered 30 years ago but initially no biologic activity was found. Further research studies discovered the presence of galanin in the brain and some peripheral tissues, and galanin was identified as a modulator of neurotransmission in the central and peripheral nervous system. Over the last decade there were performed very intensive studies of the neuronal actions and also of nonneuronal actions of galanin. Other galanin family peptides have been described, namely galanin, galanin-like peptide, galanin-message associated peptide and alarin...
July 18, 2017: Physiological Research
https://www.readbyqxmd.com/read/28730825/the-implication-of-ampa-receptor-in-synaptic-plasticity-impairment-and-intellectual-disability-in-fragile-x-syndrome
#4
G-R Cheng, X-Y Li, Y-D Xiang, D Liu, S M McClintock, Y Zeng
Fragile X syndrome (FXS) is the most frequently inherited form of intellectual disability and prevalent single-gene cause of autism. A priority of FXS research is to determine the molecular mechanisms underlying the cognitive and social functioning impairments in humans and the FXS mouse model. Glutamate ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPARs) mediate a majority of fast excitatory neurotransmission in the central nervous system and are critically important for nearly all aspects of brain function, including neuronal development, synaptic plasticity, and learning and memory...
July 18, 2017: Physiological Research
https://www.readbyqxmd.com/read/28730152/zebrafish-get-connected-investigating-neurotransmission-targets-and-alterations-in-chemical-toxicity
#5
Katharine A Horzmann, Jennifer L Freeman
Neurotransmission is the basis of neuronal communication and is critical for normal brain development, behavior, learning, and memory. Exposure to drugs and chemicals can alter neurotransmission, often through unknown pathways and mechanisms. The zebrafish (Danio rerio) model system is increasingly being used to study the brain and chemical neurotoxicity. In this review, the major neurotransmitter systems, including glutamate, GABA, dopamine, norepinephrine, serotonin, acetylcholine, histamine, and glutamate are surveyed and pathways of synthesis, transport, metabolism, and action are examined...
September 2016: Toxics
https://www.readbyqxmd.com/read/28729700/sphingomimetic-multiple-sclerosis-drug-fty720-activates-vesicular-synaptobrevin-and-augments-neuroendocrine-secretion
#6
Frederic D Darios, Jernej Jorgacevski, Ajda Flašker, Robert Zorec, Virginia García-Martinez, José Villanueva, Luis M Gutiérrez, Charlotte Leese, Manjot Bal, Elena Nosyreva, Ege T Kavalali, Bazbek Davletov
Neurotransmission and secretion of hormones involve a sequence of protein/lipid interactions with lipid turnover impacting on vesicle trafficking and ultimately fusion of secretory vesicles with the plasma membrane. We previously demonstrated that sphingosine, a sphingolipid metabolite, promotes formation of the SNARE complex required for membrane fusion and also increases the rate of exocytosis in isolated nerve terminals, neuromuscular junctions, neuroendocrine cells and in hippocampal neurons. Recently a fungi-derived sphingosine homologue, FTY720, has been approved for treatment of multiple sclerosis...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729118/hbk-14-and-hbk-15-triple-5-ht1a-5-ht7-and-5-ht3-antagonists-with-potent-antidepressant-and-anxiolytic-like-properties-increase-seizure-threshold-in-various-seizure-tests-in-mice
#7
Karolina Pytka, Katarzyna Socała, Anna Rapacz, Dorota Nieoczym, Mateusz Pieróg, Anna Gryboś, Agata Siwek, Anna Waszkielwicz, Piotr Wlaź
Most antidepressants lower seizure threshold, which might be due to the modulation of serotonergic neurotransmission. Here, we investigated the effects of two 5-HT1A, 5-HT7 and 5-HT3 antagonists, i.e., 1-[(2,6-dimethylphenoxy)ethoxyethyl]-4-(2-methoxyphenyl)piperazine hydrochloride (HBK-14) and 1-[(2-chloro-6-methylphenoxy)ethoxyethyl]-4-(2-methoxyphenyl)piperazine hydrochloride (HBK-15), with antidepressant- and anxiolytic-like properties, on seizure thresholds in three acute seizure tests, i.e., the intravenous pentylenetetrazole, maximal electroshock seizure threshold (MEST), and 6-Hz corneal stimulation test in mice...
July 17, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28729116/convergence-of-glycogen-synthase-kinase-3%C3%AE-and-gr-signaling-in-response-to-fluoxetine-treatment-in-chronically-stressed-female-and-male-rats
#8
Milos Mitic, Zeljka Brkic, Iva Lukic, Miroslav Adzic
Accumulating evidence strongly suggest that impaired glucocorticoid receptor (GR) signaling is involved in stress-related mood disorders, and nominate GR as a potential target for antidepressants (ADs). It is known that different classes of ADs affects the GR action via modifying its phosphorylation, while the mechanism through which ADs alter GR phosphorylation targeted by GSK3β, a kinase modulated via serotonin neurotransmission, are unclear. On this basis, we investigated whether GSK3β-GR signaling could be a convergence point of fluoxetine action on brain function and behavior, by examining its effect on GSK3β targeted-GR phosphorylation on threonine 171 (pGR171), and expression of GR-regulated genes in the hippocampus of female and male rats exposed to chronic isolation stress...
July 17, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28724748/depressed-synaptic-transmission-and-reduced-vesicle-release-sites-in-huntington-s-disease-neuromuscular-junctions
#9
Ahmad Khedraki, Eric J Reed, Shannon H Romer, Qingbo Wang, William Romine, Mark M Rich, Robert J Talmadge, Andrew A Voss
Huntington's disease (HD) is a progressive and fatal degenerative disorder that results in debilitating cognitive and motor dysfunction. Most HD studies have focused on degeneration of the central nervous system. We previously discovered that skeletal muscle from transgenic R6/2 HD mice is hyperexcitable due to decreased chloride and potassium conductances. The progressive and early onset of these defects suggest a primary myopathy in HD. In this study, we examined the relationship between neuromuscular transmission and skeletal muscle hyperexcitability...
July 19, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28724700/neurotransmission-peptide-transmitters-turn-36
#10
Michael P Nusbaum
No abstract text is available yet for this article.
July 15, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28723415/pharmacology-of-human-trace-amine-associated-receptors-therapeutic-opportunities-and-challenges
#11
REVIEW
Mark D Berry, Raul R Gainetdinov, Marius C Hoener, Mohammed Shahid
The discovery in 2001 of a G protein-coupled receptor family, subsequently termed trace amine-associated receptors (TAAR), triggered a resurgence of interest in so-called trace amines. Initial optimism quickly faded, however, as the TAAR family presented a series of challenges preventing the use of standard medicinal chemistry and pharmacology technologies. Consequently the development of basic tools for probing TAAR and translating findings from model systems to humans has been problematic. Despite these challenges the last 5 years have seen considerable advances, in particular with respect to TAAR1, which appears to function as an endogenous rheostat, maintaining central neurotransmission within defined physiological limits, in part through receptor heterodimerization yielding biased signaling outputs...
July 16, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28722429/detection-of-k-efflux-from-stimulated-cortical-neurons-by-an-aptamer-modified-silicon-nanowire-field-effect-transistor
#12
Ankur Anand, Chia-Rung Liu, Ai-Chuan Chou, Wan-Hsuan Hsu, Rajesh Kumar Ulaganathan, Yi-Cheng Lin, Chi-An Dai, Fan-Gang Tseng, Chien-Yuan Pan, Yit-Tsong Chen
The concentration gradient of K(+) across the cell membrane of a neuron determines its resting potential and cell excitability. During neurotransmission, the efflux of K(+) from the cell via various channels will not only decrease the intracellular K(+) content but also elevate the extracellular K(+) concentration. However, it is not clear to what extent this change could be. In this study, we developed a multiple-parallel-connected silicon nanowire field-effect transistor (SiNW-FET) modified with K(+)-specific DNA-aptamers (aptamer/SiNW-FET) for the real-time detection of the K(+) efflux from cultured cortical neurons...
January 27, 2017: ACS Sensors
https://www.readbyqxmd.com/read/28722101/-gilles-de-la-tourette-syndrome-symptoms-causes-and-therapy
#13
Ewgeni Jakubovski, Kirsten R Müller-Vahl
Gilles de la Tourette syndrome is a chronic neuropsychiatric movement disease with combined motor tics and at least one vocal tic for a minimum period of 1 year. It typically begins in the childhood (under 18 years of age).Most of the patients with Tourette syndrome have comorbidities, which often impair their quality of life more than the tics themselves.There are reported abnormalities in the cortico-striato-thalamo-cortical regions as well as in the neurotransmission of dopamine and other neurotransmission systems...
June 2017: Psychotherapie, Psychosomatik, Medizinische Psychologie
https://www.readbyqxmd.com/read/28716844/microglia-control-the-glycinergic-but-not-the-gabaergic-synapses-via-prostaglandin-e2-in-the-spinal-cord
#14
Yasmine Cantaut-Belarif, Myriam Antri, Rocco Pizzarelli, Sabrina Colasse, Ilaria Vaccari, Sylvia Soares, Marianne Renner, Radhouane Dallel, Antoine Triller, Alain Bessis
Microglia control excitatory synapses, but their role in inhibitory neurotransmission has been less well characterized. Herein, we show that microglia control the strength of glycinergic but not GABAergic synapses via modulation of the diffusion dynamics and synaptic trapping of glycine (GlyR) but not GABAA receptors. We further demonstrate that microglia regulate the activity-dependent plasticity of glycinergic synapses by tuning the GlyR diffusion trap. This microglia-synapse cross talk requires production of prostaglandin E2 by microglia, leading to the activation of neuronal EP2 receptors and cyclic adenosine monophosphate-dependent protein kinase...
July 17, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28716540/developmental-vitamin-d-deficiency-alters-multiple-neurotransmitter-systems-in-the-neonatal-rat-brain
#15
James P Kesby, Karly Turner, Suzanne Alexander, Darryl W Eyles, John J McGrath, Thomas H J Burne
BACKGROUND: Epidemiological evidence suggests that developmental vitamin D (DVD) deficiency is a risk factor for neuropsychiatric disorders, such as schizophrenia. DVD deficiency in rats is associated with altered brain structure and adult behaviours indicating alterations in dopamine and glutamate signalling. Developmental alterations in dopamine neurotransmission have also been observed in DVD-deficient rats but a comprehensive assessment of brain neurochemistry has not been undertaken...
July 14, 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28714716/cb%C3%A2-receptor-antagonism-in-the-bed-nucleus-of-the-stria-terminalis-interferes-with-affective-opioid-withdrawal-in-rats
#16
Kiri L Wills, Marieka V DeVuono, Cheryl L Limebeer, Kiran Vemuri, Alexandros Makriyannis, Linda A Parker
The bed nucleus of the stria terminalis (BNST) is a region of the extended amygdala that is implicated in addiction, anxiety, and stress related behaviors. This region has been identified in mediating the aversive state of naloxone-precipitated morphine withdrawal (MWD) and cannabinoid Type I (CB1) receptors have been found to modulate neurotransmission within this region. Previous findings suggest that the CB1 antagonist/inverse agonist, AM251, administered systemically or by infusion into the central nucleus of the amygdala (CeA) prevented the aversive affective properties of MWD as measured by conditioned place aversion learning...
August 2017: Behavioral Neuroscience
https://www.readbyqxmd.com/read/28714693/stochastic-simulation-of-dopamine-neuromodulation-for-implementation-of-fluorescent-neurochemical-probes-in-the-striatal-extracellular-space
#17
Abraham Beyene, Ian McFarlane, Rebecca Pinals, Markita P Landry
Imaging the dynamic behavior of neuromodulatory neurotransmitters in the extracelluar space arising from individual quantal releases would constitute a major advance in neurochemical imaging. Spatial and temporal resolution of these highly stochastic neuromodulatory events requires concurrent advances in the chemical development of optical nanosensors selective for neuromodulators in concert with advances in imaging methodologies to capture millisecond neurotransmitter release. Herein, we develop and implement a stochastic model to describe dopamine dynamics in the extracellular space (ECS) of the brain dorsal striatum to guide the design and implementation of fluorescent neurochemical probes that record neurotransmitter dynamics in the ECS...
July 17, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28713483/the-treadmill-exercise-protects-against-dopaminergic-neuron-loss-and-brain-oxidative-stress-in-parkinsonian-rats
#18
Roberta Oliveira da Costa, Carlos Vinicius Jataí Gadelha-Filho, Ayane Edwiges Moura da Costa, Mariana Lima Feitosa, Dayane Pessoa de Araújo, Jalles Dantas de Lucena, Pedro Everson Alexandre de Aquino, Francisco Arnaldo Viana Lima, Kelly Rose Tavares Neves, Glauce Socorro de Barros Viana
Parkinson's disease (PD), a progressive neurological pathology, presents motor and nonmotor impairments. The objectives were to support data on exercise benefits to PD. Male Wistar rats were distributed into sham-operated (SO) and 6-OHDA-lesioned, both groups without and with exercise. The animals were subjected to treadmill exercises (14 days), 24 h after the stereotaxic surgery and striatal 6-OHDA injection. Those from no-exercise groups stayed on the treadmill for the same period and, afterwards, were subjected to behavioral tests and euthanized for neurochemical and immunohistochemical assays...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28713286/mechanism-of-action-for-rtms-a-working-hypothesis-based-on-animal-studies
#19
REVIEW
Thangavelu Soundara Rajan, Maria F M Ghilardi, Hoau-Yan Wang, Emanuela Mazzon, Placido Bramanti, Domenico Restivo, Angelo Quartarone
Experiments in rodents have elucidated some of the molecular mechanisms underlying repetitive transcranial magnetic stimulation (rTMS). These studies may be useful in a translational perspective so that future TMS studies in rodents can closely match human TMS protocols designed for therapeutic purposes. In the present work we will review the effects of rTMS on glutamate neurotransmission which in turn induce persistent changes in synaptic activity. In particular, we will focus on the role of NMDA and non-NMDA transmission and on the permissive role of BDNF-TrKB interaction in the rTMS induced after-effects...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28711518/antagonism-of-the-5-ht6-receptor-preclinical-rationale-for-the-treatment-of-alzheimer-s-disease
#20
REVIEW
Inge E M de Jong, Arne Mørk
Antagonism of the 5-HT6 receptor is a promising approach for the symptomatic treatment of Alzheimer's disease (AD). There is compelling preclinical evidence for the procognitive potential of 5-HT6 receptor antagonists and several compounds are in clinical development, as adjunct therapy to acetylcholinesterase inhibitors (AChEIs). This manuscript summarizes the scientific rationale for the use of 5-HT6 receptor antagonists as AD treatment, with some focus on the selective and high-affinity 5-HT6 receptor antagonist idalopirdine (Lu AE58054)...
July 12, 2017: Neuropharmacology
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