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https://www.readbyqxmd.com/read/28087735/relationships-linking-emotional-motor-cognitive-and-gabaergic-dysfunctions-in-dystrophin-deficient-mdx-mice
#1
Cyrille Vaillend, Rémi Chaussenot
Alterations in the Duchenne muscular dystrophy (DMD) gene have been associated with enhanced stress reactivity in vertebrate species, suggesting a role for brain dystrophin in fear-related behavioral and cognitive processes. Because the loss of dystrophin (Dp427) reduces clustering of central GABAA receptors, it is suspected that local inhibitory tuning and modulation of neuronal excitability are perturbed in a distributed brain circuit that normally controls such critical behavioral functions. In this study we undertook a large-scale behavioral study to evaluate fear-related behavioral disturbances in dystrophin-deficient mdx mice...
January 13, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28077331/physiological-behavioral-changes-induced-by-a-fraction-with-antitumor-cleronade-diterpenes-from-an-atlantic-forest-brazilian-plant-and-computational-intermolecular-interactions-with-neuron-receptors
#2
Éverton José Ferreira de Araújo, Antônia Amanda Cardoso de Almeida, Oskar Almeida Silva, Iwyson Henrique Fernandes da Costa, Luis Mário Rezende Júnior, Francisco das Chagas Alves Lima, Luciano da Silva Lopes, Alberto José Cavalheiro, Paulo Michel Pinheiro Ferreira
ETHNOPHARMACOLOGICAL RELEVANCE: Casearia sylvestris is a medicinal plant traditionally used to treat snakebites, wounds, inflammation and gastric ulcers and scientific supports for have demonstrated its antitumor, antihyperlipidemic and antiparasitic properties. AIM OF THE STUDY: To assess the effects of a fraction with casearins (FC) on adult mice using classical experimental models of animal behavior and theoretical calculations to verify the interaction of Casearin X (Cas X) with neuron receptors...
January 7, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28073939/nanoscale-molecular-reorganization-of-the-inhibitory-postsynaptic-density-is-a-determinant-of-gabaergic-synaptic-potentiation
#3
Francesca Pennacchietti, Sebastiano Vascon, Thierry Nieus, Christian Rosillo, Sabyasachi Das, Shiva Tyagarajan, Alberto Diaspro, Alessio Del Bue, Enrica Maria Petrini, Andrea Barberis, Francesca Cella Zanacchi
: Gephyrin is a key scaffold protein mediating the anchoring of GABAA receptors at inhibitory synapses. Here we exploited super-resolution techniques combined with proximity-based clustering analysis and model simulations to investigate the single molecule gephyrin reorganization during plasticity of inhibitory synapses in mouse hippocampal cultured neurons. This approach revealed that during the expression of inhibitory long-term potentiation the increase of gephyrin density at postsynaptic sites is associated with the promoted formation of gephyrin nano-domains...
January 10, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28073605/comprehensive-association-analysis-of-27-genes-from-the-gabaergic-system-in-japanese-individuals-affected-with-schizophrenia
#4
Shabeesh Balan, Kazuo Yamada, Yoshimi Iwayama, Takanori Hashimoto, Tomoko Toyota, Chie Shimamoto, Motoko Maekawa, Shu Takagai, Tomoyasu Wakuda, Yosuke Kameno, Daisuke Kurita, Kohei Yamada, Mitsuru Kikuchi, Tasuku Hashimoto, Nobuhisa Kanahara, Takeo Yoshikawa
Involvement of the gamma-aminobutyric acid (GABA)-ergic system in schizophrenia pathogenesis through disrupted neurodevelopment has been highlighted in numerous studies. However, the function of common genetic variants of this system in determining schizophrenia risk is unknown. We therefore tested the association of 375 tagged SNPs in genes derived from the GABAergic system, such as GABAA receptor subunit genes, and GABA related genes (glutamate decarboxylase genes, GABAergic-marker gene, genes involved in GABA receptor trafficking and scaffolding) in Japanese schizophrenia case-control samples (n=2926; 1415 cases and 1511 controls)...
January 7, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28071892/transient-adenosine-release-is-modulated-by-nmda-and-gabab-receptors
#5
Michael D Nguyen, Ying Wang, Mallikarjunarao Ganesana, B Jill Venton
Adenosine is a neuroprotective agent that modulates neurotransmission and is modulated by other neurotransmitters. Spontaneous, transient adenosine is a recently discovered mode of signaling where adenosine is released and cleared from the extracellular space quickly, in less than three seconds. Spontaneous adenosine release is regulated by adenosine A1 and A2a receptors, but regulation by other neurotransmitter receptors has not been studied. Here, we examined the effect of glutamate and GABA receptors on the concentration and frequency of spontaneous, transient adenosine release by measuring adenosine with fast-scan cyclic voltammetry in the rat caudate-putamen...
January 10, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28069825/intravenous-anesthetic-propofol-binds-to-5-lipoxygenase-and-attenuates-leukotriene-b4-production
#6
Toshiaki Okuno, Sophia Koutsogiannaki, Mai Ohba, Matthew Chamberlain, Weiming Bu, Fu-Yan Lin, Roderic G Eckenhoff, Takehiko Yokomizo, Koichi Yuki
Propofol is an intravenous anesthetic that produces its anesthetic effect, largely via the GABAA receptor in the CNS, and also reduces the N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced neutrophil respiratory burst. Because fMLP-stimulated neutrophils produce leukotriene (LT)B4, we examined the effect of propofol on LTB4 production in vivo and in vitro Cecal ligation and puncture surgery was performed in mice, with or without exposure to propofol. Propofol attenuated the production of 5-lipoxygenase (5-LOX)-related arachidonic acid (AA) derivatives in the peritoneal fluid...
January 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28069353/effects-of-chronic-exposure-to-low-dose-thip-on-brainstem-neuronal-excitability-in-mouse-models-of-rett-syndrome-evidence-from-symptomatic-females
#7
Weiwei Zhong, Christopher Mychal Johnson, Ningren Cui, Hao Xing, Yang Wu, Chun Jiang
Rett Syndrome (RTT) is a neurodevelopmental disorder caused by mutations of the MECP2 gene, affecting predominantly females. One of the characteristic features of the disease is defective brainstem autonomic function. In Mecp2(-/Y) mice, several groups of brainstem neurons are overly excitable, which causes destabilization of neuronal networks for the autonomic control. We have previously shown that the extrasynaptic GABAA receptor agonist THIP relieves many RTT-like symptoms in Mecp2(-/Y) mice. Although neuronal activity is inhibited by acute THIP exposure, how a chronic treatment affects neuronal excitability remains elusive...
January 6, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28066142/participation-of-central-gabaa-receptors-in-the-trigeminal-processing-of-mechanical-allodynia-in-rats
#8
Min Ji Kim, Young Hong Park, Kui Ye Yang, Jin Sook Ju, Yong Chul Bae, Seong Kyu Han, Dong Kuk Ahn
Here we investigated the central processing mechanisms of mechanical allodynia and found a direct excitatory link with low-threshold input to nociceptive neurons. Experiments were performed on male Sprague-Dawley rats weighing 230-280 g. Subcutaneous injection of interleukin 1 beta (IL-1β) (1 ng/10 µL) was used to produce mechanical allodynia and thermal hyperalgesia. Intracisternal administration of bicuculline, a gamma aminobutyric acid A (GABAA) receptor antagonist, produced mechanical allodynia in the orofacial area under normal conditions...
January 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28066138/potentiation-of-decursinol-angelate-on-pentobarbital-induced-sleeping-behaviors-via-the-activation-of-gabaa-ergic-systems-in-rodents
#9
Jae Hoon Woo, Tae-Woo Ha, Jae-Seon Kang, Jin Tae Hong, Ki-Wan Oh
Angelicae Gigantis Radix (AGR, Angelica gigas) has been used for a long time as a traditional folk medicine in Korea and oriental countries. Decursinol angelate (DCA) is structurally isomeric decursin, one of the major components of AGR. This study was performed to confirm whether DCA augments pentobarbital-induced sleeping behaviors via the activation of GABAA-ergic systems in animals. Oral administration of DCA (10, 25 and 50 mg/kg) markedly suppressed spontaneous locomotor activity. DCA also prolonged sleeping time, and decreased the sleep latency by pentobarbital (42 mg/kg), in a dose-dependent manner, similar to muscimol, both at the hypnotic (42 mg/kg) and sub-hypnotic (28 mg/kg) dosages...
January 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28066107/anxiolytic-activity-of-aqueous-extract-of-camellia-sinensis-in-rats
#10
Rajeshwari Shastry, Sheetal Dinkar Ullal, Shreyas Karkala, Seema Rai, Akash Gadgade
OBJECTIVES: The present study was undertaken to evaluate anxiolytic effect of Camellia sinensis (CS) and possible mechanism on acute and chronic administration in rats. MATERIALS AND METHODS: Eight groups of rats with six in each group were used. Group I served as control. Group II received diazepam (1 mg/kg). Groups III, IV, and V received CS in doses of 3.3, 16.5, and 33 mg/kg, respectively. Three pharmacologically validated experimental models - elevated plus maze (EPM), light and dark box (LDB), and open field tests (OFT) - were employed...
November 2016: Indian Journal of Pharmacology
https://www.readbyqxmd.com/read/28065795/rational-identification-of-a-novel-soy-derived-anxiolytic-like-undecapeptide-acting-via-gut-brain-axis-after-oral-administration
#11
Ami Ota, Akane Yamamoto, Saeko Kimura, Yukiha Mori, Takafumi Mizushige, Yoshiki Nagashima, Masaru Sato, Hideyuki Suzuki, Saori Odagiri, Daisuke Yamada, Masayuki Sekiguchi, Keiji Wada, Ryuhei Kanamoto, Kousaku Ohinata
Here we found that the chymotryptic digest of soy β-conglycinin, a major storage protein, exhibited anxiolytic-like effects in mice. We then searched for anxiolytic-like peptides in the digest. Based on a comprehensive peptide analysis of the chymotryptic digest by high performance liquid chromatograph connected to an LTQ Orbitrap mass spectrometer and the structure-activity relationship of known peptides, we explored anxiolytic-like peptides present in the digest. FLSSTEAQQSY, which corresponds to 323-333 of the β-conglycinin α subunit [βCGα(323-333)] emerged as a candidate...
January 5, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28061384/oligomeric-amyloid-%C3%AE-peptide-disrupts-olfactory-information-output-by-impairment-of-local-inhibitory-circuits-in-rat-olfactory-bulb
#12
Bin Hu, Chi Geng, Xiao-Yu Hou
Although early olfactory dysfunction has been found in patients with Alzheimer's disease, the underlying mechanisms remain unclear. In this study, we investigated whether and how oligomeric amyloid-β peptide (Aβ) affects the responses of mitral cells (MCs). We found that oligomeric Aβ1-42 increased spontaneous and evoked firing rates but decreased the ratio of evoked to spontaneous firings in MCs. Aβ1-42 oligomers showed no impact on the hyperactivity exerted by pharmacological blockage of GABAA receptors, suggesting an involvement of GABAergic inhibitory transmission in Aβ1 to 42-induced over-excitability...
December 14, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/28056730/synthesis-molecular-docking-and-evaluation-of-3-4-2-amino-4-substitutedphenyl-2h-1-3-oxazin-thiazin-6-yl-2-phenyl-3h-quinazolin-4-one-derivatives-for-their-anticonvulsant-activity
#13
Nimisha Jain, Jugnu Jaiswal, Ashish Pathak, Pradeep Kumar Singour
BACKGROUND: According to World Health Organization (WHO), around 50 million people worldwide suffering from epilepsy. Therefore, continued search for safer and more effective anticonvulsants is urgently necessary. OBJECTIVES: The present work was to synthesize 2-phenyl substituted quiazolinone derivatives and to evaluate them for anticonvulsant activity and neurotoxic. METHODS: A series of novel 3-{4-[2-amino-4-(substitutedphenyl)-2H-[1.3] oxazin/thiazin-6-yl} 2-phenyl-3H-quinazolin-4-one derivatives were synthesized and evaluated for their anticonvulsant activity...
January 4, 2017: Central Nervous System Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28053010/mutations-in-gabrb3-from-febrile-seizures-to-epileptic-encephalopathies
#14
Rikke S Møller, Thomas V Wuttke, Ingo Helbig, Carla Marini, Katrine M Johannesen, Eva H Brilstra, Ulvi Vaher, Ingo Borggraefe, Inga Talvik, Tiina Talvik, Gerhard Kluger, Laurence L Francois, Gaetan Lesca, Julitta de Bellescize, Susanne Blichfeldt, Nicolas Chatron, Nils Holert, Julia Jacobs, Marielle Swinkels, Cornelia Betzler, Steffen Syrbe, Marina Nikanorova, Candace T Myers, Line H G Larsen, Sabina Vejzovic, Manuela Pendziwiat, Sarah von Spiczak, Sarah Hopkins, Holly Dubbs, Yuan Mang, Konstantin Mukhin, Hans Holthausen, Koen L van Gassen, Hans A Dahl, Niels Tommerup, Heather C Mefford, Guido Rubboli, Renzo Guerrini, Johannes R Lemke, Holger Lerche, Hiltrud Muhle, Snezana Maljevic
OBJECTIVE: To examine the role of mutations in GABRB3 encoding the β3 subunit of the GABAA receptor in individual patients with epilepsy with regard to causality, the spectrum of genetic variants, their pathophysiology, and associated phenotypes. METHODS: We performed massive parallel sequencing of GABRB3 in 416 patients with a range of epileptic encephalopathies and childhood-onset epilepsies and recruited additional patients with epilepsy with GABRB3 mutations from other research and diagnostic programs...
January 4, 2017: Neurology
https://www.readbyqxmd.com/read/28045167/cdc20sirna-and-paclitaxel-co-loaded-nanometric-liposomes-of-a-nipecotic-acid-derived-cationic-amphiphile-inhibit-xenografted-neuroblastoma
#15
Sukanya Bhunia, Vegesna Radha, Arabinda Chaudhuri
Despite significant recent progress in the area of translational genomics of neuroblastoma, the overall survival rates for children with high-risk NB continue to be not more than 5 years due to tumor relapse and/or drug-resistant tumors. Herein we report on the development of a neuroblastoma targeting nanometric (130-150 nm) circulation stable liposomal system prepared from a novel nipecotic acid-derived cationic amphiphile (NACA). The size ranges of liposomes (130-150 nm) were confirmed by both dynamic light scattering and transmission electron microscopy...
January 3, 2017: Nanoscale
https://www.readbyqxmd.com/read/28035673/somatic-and-neuritic-spines-on-tyrosine-hydroxylase-immunopositive-cells-of-rat-retina
#16
Anna Fasoli, James Dang, Aaron H Gouw, Jeffrey S Johnson, Alex Fogli Iseppe, Andrew T Ishida
Dopamine- and tyrosine hydroxylase-immunopositive cells (TH cells) modulate visually driven signals as they flow through retinal photoreceptor, bipolar, and ganglion cells. Previous studies suggested that TH cells release dopamine from varicose axons arborizing in the inner and outer plexiform layers after glutamatergic synapses depolarize TH cell dendrites in the inner plexiform layer and these depolarizations propagate to the varicosities. Although it has been proposed that these excitatory synapses are formed onto appendages resembling dendritic spines, spines have not been found on TH cells of most species examined to date or on TH cell somata which release dopamine when exposed to glutamate receptor agonists...
December 30, 2016: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28032294/examination-of-the-role-of-nmda-and-gabaa-receptors-in-the-effects-of-hyperbaric-oxygen-on-striatal-dopamine-levels-in-rats
#17
C Lavoute, M Weiss, J J Risso, J C Rostain
Hyperbaric oxygen induced in rats a decrease in striatal dopamine levels. Such decrease could be a result of changes in glutamatergic and GABAergic controls of the dopaminergic neurons into the Substantia Nigra Pars Compacta. The aim of this study was to determine the role of gluatamatergic and Gama-Amino-Butyric-Acid neurotransmissions in this alteration. Dopamine-sensitive electrodes were implanted into the striatum under general anesthesia. After one week rest, awaked rats were exposed to oxygen-nitrogen mixture at a partial pressure of oxygen of 3 absolute atmospheres...
December 28, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/28032116/synaptic-inhibition-in-avian-interaural-level-difference-sound-localizing-neurons
#18
Rebecca J Curry, Yong Lu
Synaptic inhibition plays a fundamental role in the neural computation of the interaural level difference (ILD), an important cue for the localization of high-frequency sound. Here, we studied the inhibitory synaptic currents in the chicken posterior portion of the dorsal nucleus of the lateral lemniscus (LLDp), the first binaural level difference encoder of the avian auditory pathway. Using whole-cell recordings in brain slices, we provide the first evidence confirming a monosynaptic inhibition driven by direct electrical and chemical stimulation of the contralateral LLDp, establishing the reciprocal inhibitory connection between the two LLDps, a long-standing assumption in the field...
November 2016: ENeuro
https://www.readbyqxmd.com/read/28031402/presynaptic-gain-control-by-endogenous-cotransmission-of-dopamine-and-gaba-in-the-olfactory-bulb
#19
Christopher E Vaaga, Jordan T Yorgason, John T Williams, Gary L Westbrook
In the olfactory bulb, lateral inhibition mediated by local juxtaglomerular interneurons has been proposed as a gain control mechanism, important for de-correlating odorant responses. Among juxtaglomerular interneurons, short axon cells are unique as dual-transmitter neurons that release dopamine and GABA. To examine their intraglomerular function, we expressed channelrhodopsin under control of the DAT-cre promoter, and activated olfactory afferents within individual glomeruli. Optical stimulation of labeled cells triggered endogenous dopamine release as measured by cyclic voltammetry, and GABA release as measured by whole-cell GABAA receptor currents...
December 28, 2016: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28013354/gabaa-receptor-occupancy-by-subtype-selective-gabaa%C3%AE-2-3-modulators-pet-studies-in-humans
#20
Aurelija Jucaite, Zsolt Cselényi, Jaakko Lappalainen, Dennis J McCarthy, Chi-Ming Lee, Svante Nyberg, Katarina Varnäs, Per Stenkrona, Christer Halldin, Alan Cross, Lars Farde
RATIONALE: Sedation, dependence, and abuse liability limit the use of non-selective γ-aminobutyric acid (GABAA) receptor positive modulators for the treatment of anxiety. AZD7325 and AZD6280 are novel, subtype-selective GABAAα2,3 receptor positive modulators with limited sedative effects. OBJECTIVES: The current study aimed to confirm target engagement at GABAA receptors by AZD7325 and AZD6280 in humans and to determine the relationship between exposure, GABAA receptor occupancy, and tolerability...
December 24, 2016: Psychopharmacology
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