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https://www.readbyqxmd.com/read/28424564/new-developments-in-the-management-of-narcolepsy
#1
REVIEW
Vivien C Abad, Christian Guilleminault
Narcolepsy is a life-long, underrecognized sleep disorder that affects 0.02%-0.18% of the US and Western European populations. Genetic predisposition is suspected because of narcolepsy's strong association with HLA DQB1*06-02, and genome-wide association studies have identified polymorphisms in T-cell receptor loci. Narcolepsy pathophysiology is linked to loss of signaling by hypocretin-producing neurons; an autoimmune etiology possibly triggered by some environmental agent may precipitate hypocretin neuronal loss...
2017: Nature and Science of Sleep
https://www.readbyqxmd.com/read/28424220/gababr-induced-egfr-transactivation-promotes-migration-of-human-prostate-cancer-cells
#2
Shuai Xia, Cong He, Yini Zhu, Suyun Wang, Huiping Li, Zhongling Zhang, Xinnong Jiang, Jianfeng Liu
G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs) act in concert to regulate cell growth, proliferation, survival, and migration. Metabotropic GABAB receptor (GABABR) is the GPCR for the main inhibitory neurotransmitter GABA in the central nervous system. Increased expression of GABABR has been detected in human cancer tissues and cancer cell lines, but the role of GABABR in these cells is controversial and the underlying mechanism remains poorly understood. Here, we investigated whether GABABR hijacks RTK signaling to modulate the fates of human prostate cancer cells...
April 19, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28419642/nicotine-induced-molecular-alterations-are-modulated-by-gabab-receptor-activity
#3
Andres P Varani, Valeria T Pedrón, Amira J Aon, Christian Höcht, Gabriela B Acosta, Bernhard Bettler, Graciela N Balerio
It has been demonstrated that GABAB receptors modulate nicotine (NIC) reward effect; nevertheless, the mechanism implicated is not well known. In this regard, we evaluated the involvement of GABAB receptors on the behavioral, neurochemical, biochemical and molecular alterations associated with the rewarding effects induced by NIC in mice, from a pharmacological and genetic approach. NIC-induced rewarding properties (0.5 mg/kg, subcutaneously, sc) were evaluated by conditioned place preference (CPP) paradigm...
April 17, 2017: Addiction Biology
https://www.readbyqxmd.com/read/28419057/gabaergic-modulation-of-noradrenaline-release-caused-by-blood-pressure-changes-in-the-rat-median-preoptic-area
#4
Makoto Takahashi, Junichi Tanaka
Experiments using in-vivo microdialysis methods were conducted to investigate whether blood pressure changes cause an alteration in the release of noradrenaline (NA) in the median preoptic nucleus (MnPO) and whether the γ-aminobutyric acid (GABA) receptor mechanism is involved in the modulation of the pressure response-induced alteration in the NA release. In urethane-anesthetized male rats, intravenous administration of metaraminol, an α-agonist, significantly produced an increase in dialysate NA concentration in the MnPO area accompanied by an elevation in the mean arterial pressure (MAP)...
April 17, 2017: Neuroreport
https://www.readbyqxmd.com/read/28416021/effects-of-gabab-receptors-in-the-insula-on-recognition-memory-observed-with-intellicage
#5
Nan Wu, Feng Wang, Zhe Jin, Zhen Zhang, Lian-Kun Wang, Chun Zhang, Tao Sun
BACKGROUND: Insular function has gradually become a topic of intense study in cognitive research. Recognition memory is a commonly studied type of memory in memory research. GABABR has been shown to be closely related to memory formation. In the present study, we used intellicage, which is a new intelligent behavioural test system, and a bilateral drug microinjection technique to inject into the bilateral insula, to examine the relationship between GABABR and recognition memory. METHODS: Male Sprague-Dawley rats were randomly divided into control, Sham, Nacl, baclofen and CGP35348 groups...
April 17, 2017: Behavioral and Brain Functions: BBF
https://www.readbyqxmd.com/read/28400257/phase-amplitude-coupled-persistent-theta-and-gamma-oscillations-in-rat-primary-motor-cortex-in-vitro
#6
Nicholas W Johnson, Mazhar Özkan, Adrian P Burgess, Emma J Prokic, Keith A Wafford, Michael J O'Neill, Stuart D Greenhill, Ian M Stanford, Gavin L Woodhall
In vivo, theta (4-7 Hz) and gamma (30-80 Hz) neuronal network oscillations are known to coexist and display phase-amplitude coupling (PAC). However, in vitro, these oscillations have for many years been studied in isolation. Using an improved brain slice preparation technique we have, using co-application of carbachol (10 μM) and kainic acid (150 nM), elicited simultaneous theta (6.6 ± 0.1 Hz) and gamma (36.6 ± 0.4 Hz) oscillations in rodent primary motor cortex (M1). Each oscillation showed greatest power in layer V...
April 8, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28395176/the-ketogenic-diet-metabolite-beta-hydroxybutyrate-%C3%AE-hb-reduces-incidence-of-seizure-like-activity-sla-in-a-katp-and-gabab-dependent-manner-in-a-whole-animal-drosophila-melanogaster-model
#7
Jinglu Li, Emma I O'Leary, Geoffrey R Tanner
The high-fat, low-carbohydrate ketogenic diet (KD) is an effective clinical treatment for epilepsy in juveniles, especially for drug-resistant seizures. The KD results in elevated production of ketone bodies (KB's), such as beta-hydroxybutyrate (β-HB), which are thought to have anticonvulsant properties; however, their exact mechanism of action is unknown. In vitro, KB effects on reducing neuronal firing rates are mediated in part by Katp channel activity and GABAb signaling. In order to study metabolic and pharmacological effects in a whole-animal model, we used the eas "bang-sensitive" (BS) mutant strain of Drosophila, which exhibits seizure-like activity (SLA) upon mechanical stimulation...
April 5, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28382542/kk-92a-a-novel-gabab-receptor-positive-allosteric-modulator-attenuates-nicotine-self-administration-and-cue-induced-nicotine-seeking-in-rats
#8
Xia Li, Emmanuel Sturchler, Katarzyna Kaczanowska, Michael Cameron, M G Finn, Patrick Griffin, Patricia McDonald, Athina Markou
RATIONALE: GABAB receptors (GABABR) play a critical role in GABAergic neurotransmission in the brain and are thought to be one of the most promising targets for the treatment of drug addiction. GABABR positive allosteric modulators (PAMs) have shown promise as potential anti-addictive therapies, as they lack the sedative and muscle relaxant properties of full GABAB receptor agonists such as baclofen. OBJECTIVES: The present study was aimed at developing novel, selective, and potent GABABR PAMs with efficacy on abuse-related effects of nicotine...
April 5, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28361168/influence-of-leptin-and-gabab-receptor-agonist-and-antagonist-on-neurons-of-the-hypothalamic-infundibular-nucleus-in-the-chicken
#9
S Bogatyrev, K S Yakimova, B Tzschentke
In birds and mammals, the neuroendocrine regulation of energy balance is conserved in many aspects. Despite significant similarities between the two groups, differences in the regulatory mechanisms were detected. The present study was performed to carry out investigations of the influence of human leptin and GABAB-receptor agonist and antagonist on the firing rate of neurons of the Nucleus infundibuli hypothalami in brain slices from juvenile chickens. For the first time, we demonstrated a clear, dose-related change in the firing rate of hypothalamic neurons in juvenile chickens after the acute application of recombinant human leptin (1, 10, and 100 nM)...
March 30, 2017: Journal of Comparative Physiology. A, Neuroethology, Sensory, Neural, and Behavioral Physiology
https://www.readbyqxmd.com/read/28359285/atypical-periodic-alternating-nystagmus-responding-to-high-dose-intravenous-immunoglobulins-a-case-report
#10
Herminia Argente-Escrig, Luis Bataller, Claudio Krstulovic Roa, Vanesa Pérez Guillén, Herminio Perez Garrigues, Bonaventura Casanova Estruch
BACKGROUND: Acquired periodic alternating nystagmus (PAN) is a rare but well-defined syndrome that consists of a horizontal nystagmus that cyclically reverses its direction. PAN can be caused by degenerative, neoplastic, or toxic diseases of the cerebellum and, in a few cases, by subacute cerebellar ataxia of immune origin. CASE PRESENTATION: A 44-year-old man came to our attention because of rapidly progressive gait instability and blurred vision. Clinical examination showed PAN and a mild pancerebellar syndrome...
March 31, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28357120/gabab-receptor-allosteric-modulators-exhibit-pathway-dependent-and-species-selective-activity
#11
Emmanuel Sturchler, Xia Li, Maria de Lourdes Ladino, Kasia Kaczanowska, Michael Cameron, Patrick R Griffin, M G Finn, Athina Markou, Patricia McDonald
Positive modulation of the GABAB receptor (GABABR) represents a potentially useful therapeutic approach for the treatment of nicotine addiction. The positive allosteric modulators (PAMs) of GABABR GS39783 and BHF177 enhance GABA-stimulated [(35)S]GTP γS-binding, and have shown efficacy in a rodent nicotine self-administration procedure reflecting aspects of nicotine dependence. Interestingly, the structural related analog, NVP998, had no effect on nicotine self-administration in rats despite demonstrating similar pharmacokinetic properties...
April 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28348006/gabab-receptor-attenuation-of-gabaa-currents-in-neurons-of-the-mammalian-central-nervous-system
#12
Wen Shen, Changlong Nan, Peter T Nelson, Harris Ripps, Malcolm M Slaughter
Ionotropic receptors are tightly regulated by second messenger systems and are often present along with their metabotropic counterparts on a neuron's plasma membrane. This leads to the hypothesis that the two receptor subtypes can interact, and indeed this has been observed in excitatory glutamate and inhibitory GABA receptors. In both systems the metabotropic pathway augments the ionotropic receptor response. However, we have found that the metabotropic GABAB receptor can suppress the ionotropic GABAA receptor current, in both the in vitro mouse retina and in human amygdala membrane fractions...
March 2017: Physiological Reports
https://www.readbyqxmd.com/read/28342823/evidence-that-increased-kcnj6-gene-dose-is-necessary-for-deficits-in-behavior-and-dentate-gyrus-synaptic-plasticity-in-the-ts65dn-mouse-model-of-down-syndrome
#13
Alexander M Kleschevnikov, Jessica Yu, Jeesun Kim, Larisa V Lysenko, Zheng Zeng, Y Eugene Yu, William C Mobley
Down syndrome (DS), trisomy 21, is caused by increased dose of genes present on human chromosome 21 (HSA21). The gene-dose hypothesis argues that a change in the dose of individual genes or regulatory sequences on HSA21 is necessary for creating DS-related phenotypes, including cognitive impairment. We focused on a possible role for Kcnj6, the gene encoding Kir3.2 (Girk2) subunits of a G-protein-coupled inwardly-rectifying potassium channel. This gene resides on a segment of mouse Chromosome 16 that is present in one extra copy in the genome of the Ts65Dn mouse, a well-studied genetic model of DS...
March 22, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28331010/presynaptic-and-extrasynaptic-regulation-of-posterior-nucleus-of-thalamus
#14
Anthony Park, Ying Li, Radi Masri, Asaf Keller
The posterior nucleus of thalamus (PO) is a higher-order nucleus involved in sensorimotor processing, including nociception. An important characteristic of PO is its wide range of activity profiles that vary across states of arousal, thought to underlie differences in somatosensory perception subject to attention and degree of consciousness. Further, PO loses the ability to down-regulate its activity level in some forms of chronic pain, suggesting that regulatory mechanisms underlying the normal modulation of PO activity may be pathologically altered...
March 22, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28324056/gabaergic-neurons-and-their-modulatory-effects-on-gnrh3-in-zebrafish
#15
Yanlong Song, Binbin Tao, Ji Chen, Shaoting Jia, Zuoyan Zhu, Vance L Trudeau, Wei Hu
γ-Aminobutyric acid (GABA) is a major amino acid neurotransmitter in the vertebrate brain. To provide detailed information on the distribution of the GABA in zebrafish (Danio rerio), neurons were labeled with mCherry driven by the glutamic acid decarboxylase 67 (gad67) promoter. In the transgenic line Tg(gad67:mCherry), mCherry-positive gad67 cell bodies were predominantly localized to the olfactory bulb, pallial zones, subpallium zones, parvocellular preoptic nucleus, periventricular gray zone of optic tectum, torus semicircularis, posterior tuberculum, medial longitudinal fascicle, caudal zone of periventricular hypothalamus, and oculomotor nucleus...
April 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323850/ligand-guided-homology-modelling-of-the-gabab2-subunit-of-the-gabab-receptor
#16
Thibaud Freyd, Dawid Warszycki, Stefan Mordalski, Andrzej J Bojarski, Ingebrigt Sylte, Mari Gabrielsen
γ-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the central nervous system, and disturbances in the GABAergic system have been implicated in numerous neurological and neuropsychiatric diseases. The GABAB receptor is a heterodimeric class C G protein-coupled receptor (GPCR) consisting of GABAB1a/b and GABAB2 subunits. Two GABAB receptor ligand binding sites have been described, namely the orthosteric GABA binding site located in the extracellular GABAB1 Venus fly trap domain and the allosteric binding site found in the GABAB2 transmembrane domain...
2017: PloS One
https://www.readbyqxmd.com/read/28323246/the-role-of-spinal-gabab-receptors-in-cancelr-induced-bone-pain-in-rats
#17
Ya-Qun Zhou, Shu-Ping Chen, Dai-Qiang Liu, Anne Manyande, Wen Zhang, Shao-Bing Yang, Bing-Rui Xiong, Qiao-Chu Fu, Zhen-Peng Song, Heike Rittner, Da-Wei Ye, Yu-Ke Tian
Cancer-induced bone pain (CIBP) remains a major challenge in advanced cancer patients due to our lack of understanding of its mechanisms. Previous studies have demonstrated the vital role of GABAB receptors (GABABRs) in regulating nociception and various neuropathic pain models have shown diminished activity of GABABRs. However, the role of spinal GABABRs in CIBP remains largely unknown. In this study, we investigated the specific cellular mechanisms of GABABRs in the development and maintenance of CIBP in rats...
March 18, 2017: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28320266/mechanisms-of-long-term-plasticity-of-hippocampal-gabaergic-synapses
#18
REVIEW
A V Rozov, F F Valiullina, A P Bolshakov
Long-term potentiation and depression of synaptic transmission have been considered as cellular mechanisms of memory in studies conducted in recent decades. These studies were predominantly focused on mechanisms underlying plasticity at excitatory synapses. Nevertheless, normal central nervous system functioning requires maintenance of a balance between inhibition and excitation, suggesting existence of similar modulation of glutamatergic and GABAergic synapses. Here we review the involvement of G-protein-coupled receptors in the generation of long-term changes in synaptic transmission of inhibitory synapses...
March 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28316115/gabaa-and-gabab-receptor-dysregulation-in-superior-frontal-cortex-of-subjects-with-schizophrenia-and-bipolar-disorder
#19
S Hossein Fatemi, Timothy D Folsom, Paul D Thuras
Schizophrenia and bipolar disorder are complex psychiatric disorders that affect millions of people worldwide. Evidence from gene association and postmortem studies has identified abnormalities of the gamma-aminobutyric acid (GABA) signaling system in both disorders. Abnormal GABAergic signaling and transmission could contribute to the symptomatology of these disorders, potentially through impaired gamma oscillations which normally occur during cognitive processing. In the current study, we examined the protein expression of 14 GABAA and two GABAB receptor subunits in the superior frontal cortex of subjects with schizophrenia, bipolar disorder, and healthy controls...
March 18, 2017: Synapse
https://www.readbyqxmd.com/read/28299422/homeostatic-regulation-through-gaba-and-acetylcholine-muscarinic-receptors-of-motor-trigeminal-neurons-following-sleep-deprivation
#20
Hanieh Toossi, Esther Del Cid-Pellitero, Barbara E Jones
Muscle tone is regulated across sleep-wake states, being maximal in waking, reduced in slow wave sleep (SWS) and absent in paradoxical or REM sleep (PS or REMS). Such changes in tone have been recorded in the masseter muscles and shown to correspond to changes in activity and polarization of the trigeminal motor 5 (Mo5) neurons. The muscle hypotonia and atonia during sleep depend in part on GABA acting upon both GABAA and GABAB receptors (Rs) and acetylcholine (ACh) acting upon muscarinic 2 (AChM2) Rs. Here, we examined whether Mo5 neurons undergo homeostatic regulation through changes in these inhibitory receptors following prolonged activity with enforced waking...
March 15, 2017: Brain Structure & Function
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