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https://www.readbyqxmd.com/read/29331264/altered-levels-of-the-splicing-factor-muscleblind-modifies-cerebral-cortical-function-in-mouse-models-of-myotonic-dystrophy
#1
Gang Chen, Russell E Carter, John D Cleary, Tammy S Reid, Laura P Ranum, Maurice S Swanson, Timothy J Ebner
Myotonic dystrophy (DM) is a progressive, multisystem disorder affecting skeletal muscle, heart, and central nervous system. In both DM1 and DM2, microsatellite expansions of CUG and CCUG RNA repeats, respectively, accumulate and disrupt functions of alternative splicing factors, including muscleblind (MBNL) proteins. Grey matter loss and white matter changes, including the corpus callosum, likely underlie cognitive and executive function deficits in DM patients. However, little is known how cerebral cortical circuitry changes in DM...
January 10, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29330041/acute-epileptiform-activity-induced-by-gabazine-involves-proteasomal-rather-than-lysosomal-degradation-of-kca2-2-channels
#2
Steffen Müller, Xiati Guli, Judith Hey, Anne Einsle, Daniela Pfanz, Victor Sudmann, Timo Kirschstein, Rüdiger Köhling
Voltage-independent, Ca2+-activated K+ channels (KCa2.2, previously named SK2) are typically activated during a train of action potentials, and hence, are powerful regulators of cellular excitability by generating an afterhyperpolarizing potential (AHP) following prolonged excitation. In the acute in vitro epilepsy model induced in hippocampal brain slice preparations by exposure to the GABAA receptor blocker gabazine (GZ), the AHP was previously shown to be significantly decreased. Here, we asked the question whether KCa2...
January 9, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29329909/the-signaling-role-for-chloride-in-the-bidirectional-communication-between-neurons-and-astrocytes
#3
REVIEW
Corinne S Wilson, Alexander A Mongin
It is well known that the electrical signaling in neuronal networks is modulated by chloride (Cl-) fluxes via the inhibitory GABAA and glycine receptors. Here, we discuss the putative contribution of Cl- fluxes and intracellular Cl- to other forms of information transfer in the CNS, namely the bidirectional communication between neurons and astrocytes. The manuscript (i) summarizes the generic functions of Cl- in cellular physiology, (ii) recaps molecular identities and properties of Cl- transporters and channels in neurons and astrocytes, and (iii) analyzes emerging studies implicating Cl- in the modulation of neuroglial communication...
January 9, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29325900/orexin-b-modulates-synaptic-transmission-of-rod-bipolar-cells-in-rat-retina
#4
Gong Zhang, Xiao-Hua Wu, Guo-Zhong Xu, Shi-Jun Weng, Xiong-Li Yang, Yong-Mei Zhong
Orexin-A, -B play a crucial role in arousal and feeding by activating two G-protein-coupled receptors: orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R). Orexins, along with orexin receptors, are expressed in retinal neurons, and they have been shown to differentially modulate excitatory AMPA receptors of amacrine and ganglion cells in the inner retina. In this work we report that orexin-B modulates the activity of rod bipolar cells (RBCs) located in the outer retina of rat. Intravitreal injection of orexin-B increased the amplitude of the scotopic electroretinographic b-wave, a reflection of RBC activity, recorded in vivo...
January 8, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29316656/azemiopsin-a-selective-peptide-antagonist-of-muscle-nicotinic-acetylcholine-receptor-preclinical-evaluation-as-a-local-muscle-relaxant
#5
Irina V Shelukhina, Maxim N Zhmak, Alexander V Lobanov, Igor A Ivanov, Alexandra I Garifulina, Irina N Kravchenko, Ekaterina A Rasskazova, Margarita A Salmova, Elena A Tukhovskaya, Vladimir A Rykov, Gulsara A Slashcheva, Natalya S Egorova, Inessa S Muzyka, Victor I Tsetlin, Yuri N Utkin
Azemiopsin (Az), a linear peptide from the Azemiops feae viper venom, contains no disulfide bonds, is a high-affinity and selective inhibitor of nicotinic acetylcholine receptor (nAChR) of muscle type and may be considered as potentially applicable nondepolarizing muscle relaxant. In this study, we investigated its preclinical profile in regard to in vitro and in vivo efficacy, acute and chronic toxicity, pharmacokinetics, allergenic capacity, immunotoxicity and mutagenic potency. The peptide effectively inhibited (IC50 ~ 19 nM) calcium response of muscle nAChR evoked by 30 μM (EC100) acetylcholine but was less potent (IC50 ~ 3 μM) at α7 nAChR activated by 10 μM (EC50) acetylcholine and had a low affinity to α4β2 and α3-containing nAChR, as well as to GABAA or 5HT₃ receptors...
January 7, 2018: Toxins
https://www.readbyqxmd.com/read/29316237/administration-of-alphas1-casein-hydrolysate-increases-sleep-and-modulates-gabaa-receptor-subunit-expression
#6
Taddesse Yayeh, Yea-Hyun Leem, Kyung-Mi Kim, Jae-Chul Jung, Jessica Schwarz, Ki-Wan Oh, Seikwan Oh
Sleep is the most basic and essential physiological requirement for mental health, and sleep disorders pose potential risks of metabolic and neurodegenerative diseases. Tryptic hydrolysate of αS1-casein (αS1-CH) has been shown to possess stress relieving and sleep promoting effects. However, the differential effects of αS1-CH on electroencephalographic wave patterns and its effects on the protein levels of γ-aminobutyric acid A (GABAA) receptor subtypes in hypothalamic neurons are not well understood. We found αS1-CH (120, 240 mg/kg) increased sleep duration in mice and reduced sleep-wake cycle numbers in rats...
January 9, 2018: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29314165/synthesis-of-c-14-labeled-gabaa-%C3%AE-2-%C3%AE-3-selective-partial-agonists-and-the-investigation-of-late-occurring-and-long-circulating-metabolites-of-gabaa-receptor-modulator-azd7325
#7
Markus Artelsmair, Chungang Gu, Richard J Lewis, Charles S Elmore
Anxiolytic activity has been associated with GABAA α2 and α3 subunits. Several target compounds were identified and required in C-14 labeled form to enable a better understanding of their DMPK properties. AZD7325 is a selective GABAA α2 and α3 receptor modulator intended for the treatment of anxiety through oral administration. A great number of AZD7325 metabolites were observed across species in vivo, whose identification was aided by [14 C]AZD7325. An interesting metabolic cyclization and aromatization pathway leading to the tricyclic core of M9 and the oxidative pathways to M10 and M42 are presented...
January 4, 2018: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/29311144/differentiation-and-characterization-of-excitatory-and-inhibitory-synapses-by-cryo-electron-tomography-and-correlative-microscopy
#8
Chang-Lu Tao, Yun-Tao Liu, Rong Sun, Bin Zhang, Lei Qi, Sakar Shivakoti, Chong-Li Tian, Peijun Zhang, Pak-Ming Lau, Z Hong Zhou, Guo-Qiang Bi
As key functional units in neural circuits, different types of neuronal synapses play distinct roles in brain information processing, learning and memory. Synaptic abnormalities are believed to underlie various neurological and psychiatric disorders. Here, by combining cryo-electron tomography and cryo-correlative light and electron microscopy, we distinguished intact excitatory and inhibitory synapses of cultured hippocampal neurons, and visualized the in situ three-dimensional organization of synaptic organelles and macromolecules in their native state...
January 8, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29311142/regulation-of-lateral-hypothalamic-orexin-activity-by-local-gabaergic-neurons
#9
Loris L Ferrari, Daniel Park, Lin Zhu, Matthew R Palmer, Rebecca Y Broadhurst, Elda Arrigoni
Orexin (also known as hypocretin) neurons are considered a key component of the ascending arousal system. They are active during wakefulness, at which time they drive and maintain arousal, and are silent during sleep. Their activity is controlled by long-range inputs from many sources, as well as by more short-range inputs, including from presumptive GABAergic neurons in the lateral hypothalamus/perifornical region (LH/PF). To characterize local GABAergic input to orexin neurons we employed channelrhodopsin-2 (ChR2)-assisted-circuit-mapping in brain slices...
January 8, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29310424/evodiamine-reduces-caffeine-induced-sleep-disturbances-and-excitation-in-mice
#10
Yong-Hyun Ko, Kyu-Yeon Shim, Seok-Yong Lee, Choon-Gon Jang
Worldwide, caffeine is among the most commonly used stimulatory substances. Unfortunately, significant caffeine consumption is associated with several adverse effects, ranging from sleep disturbances (including insomnia) to cardiovascular problems. This study investigates whether treatment with the Evodia rutaecarpa aqueous extract (ERAE) from berries and its major molecular component, evodiamine, can reduce the adverse caffeine-induced sleep-related and excitation effects. We combined measurements from the pentobarbital-induced sleep test, the open field test, and the locomotor activity test in mice that had been dosed with caffeine...
January 9, 2018: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29302615/homeostatic-changes-in-gaba-and-acetylcholine-muscarinic-receptors-on-gabaergic-neurons-in-the-mesencephalic-reticular-formation-following-sleep-deprivation
#11
Hanieh Toossi, Esther Del Cid-Pellitero, Barbara E Jones
We have examined whether GABAergic neurons in the mesencephalic reticular formation (RFMes), which are believed to inhibit the neurons in the pons that generate paradoxical sleep (PS or REMS), are submitted to homeostatic regulation under conditions of sleep deprivation (SD) by enforced waking during the day in mice. Using immunofluorescence, we investigated first, by staining for c-Fos, whether GABAergic RFMes neurons are active during SD and then, by staining for receptors, whether their activity is associated with homeostatic changes in GABAA or acetylcholine muscarinic type 2 (AChM2) receptors (Rs), which evoke inhibition...
November 2017: ENeuro
https://www.readbyqxmd.com/read/29298431/postsynaptic-gababrs-inhibit-l-type-calcium-channels-and-abolish-long-term-potentiation-in-hippocampal-somatostatin-interneurons
#12
Sam A Booker, Desiree Loreth, Annabelle L Gee, Masahiko Watanabe, Peter C Kind, David J A Wyllie, Ákos Kulik, Imre Vida
Inhibition provided by local GABAergic interneurons (INs) activates ionotropic GABAA and metabotropic GABAB receptors (GABABRs). Despite GABABRs representing a major source of inhibition, little is known of their function in distinct IN subtypes. Here, we show that, while the archetypal dendritic-inhibitory somatostatin-expressing INs (SOM-INs) possess high levels of GABABR on their somato-dendritic surface, they fail to produce significant postsynaptic inhibitory currents. Instead, GABABRs selectively inhibit dendritic CaV1...
January 2, 2018: Cell Reports
https://www.readbyqxmd.com/read/29289597/hippocampal-gabaa-antagonism-reverses-the-novel-object-recognition-deficit-in-sub-chronic-phencyclidine-treated-rats
#13
Nichole M Neugebauer, Masanori Miyauchi, Tatsuya Sato, Jun Tadano, Hanife Akal, Hossein Ardehali, Herbert Y Meltzer
BACKGROUND: Abnormalities in prefrontal cortical and hippocampal GABAergic function are postulated to be major causes of the cognitive impairment associated with schizophrenia (CIAS). There are conflicting views on whether diminished or enhanced GABAergic activity contributes to the deficit in short-term novel object recognition (NOR) in the sub-chronic phencyclidine (scPCP) rodent model of CIAS. This study assessed the role of GABAA signaling in the medial prefrontal cortex (mPFC) and ventral hippocampus (vHPC) in NOR in saline (scSAL)- and scPCP-treated rats...
December 28, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/29283314/delayed-inhibition-of-tonic-inhibition-enhances-functional-recovery-following-experimental-ischemic-stroke
#14
James E Orfila, Himmat Grewal, Robert M Dietz, Frank Strnad, Takeru Shimizu, Myriam Moreno, Christian Schroeder, Joan Yonchek, Krista M Rodgers, Andra Dingman, Timothy J Bernard, Nidia Quillinan, Wendy B Macklin, Richard J Traystman, Paco S Herson
The current study focuses on the ability to improve cognitive function after stroke with interventions administered at delayed/chronic time points. In light of recent studies demonstrating delayed GABA antagonists improve motor function, we utilized electrophysiology, biochemistry and neurobehavioral methods to investigate the role of α5 GABAA receptors on hippocampal plasticity and functional recovery following ischemic stroke. Male C57Bl/6 mice were exposed to 45 min transient middle cerebral artery occlusion and analysis of synaptic and functional deficits performed 7 or 30 days after recovery...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29283181/loss-of-constitutive-functional-%C3%AE-aminobutyric-acid-type-a-b-receptor-crosstalk-in-layer-5-pyramidal-neurons-of-human-epileptic-temporal-cortex
#15
Katiuscia Martinello, Miriam Sciaccaluga, Roberta Morace, Addolorata Mascia, Antonietta Arcella, Vincenzo Esposito, Sergio Fucile
OBJECTIVE: γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in adult central nervous system, and profound alterations of GABA receptor functions are linked to temporal lobe epilepsy (TLE). Here we describe the functional relationships between GABA receptors type B (GABAB R) and type A (GABAA R) in human temporal cortex and how TLE affects this aspect of GABAergic signaling. METHODS: Miniature inhibitory postsynaptic currents (mIPSCs) were recorded by patch-clamp techniques from human L5 pyramidal neurons in slices from temporal cortex tissue obtained from surgery...
December 28, 2017: Epilepsia
https://www.readbyqxmd.com/read/29282556/identification-and-expression-of-a-unique-neonatal-variant-of-the-gabaa-receptor-%C3%AE-3-subunit
#16
Stephanie M Miller, Samuel Pelly, Viskasari P Kalanjati, Aven Lee, Paul B Colditz, S Tracey Bjorkman
The GABAA receptor provides the majority of inhibitory neurotransmission in the adult central nervous system but in immature brain is responsible for much of the excitatory drive, a requirement for normal brain development. It is well established that GABAA receptor subunit expression changes across the course of brain development. In the present study, we have identified a splice variant of the GABAA receptor α3 subunit which appears unique to the developing brain, referred to here as the GABAA receptor α3 subunit neonatal variant (GABAA receptor α3N)...
December 27, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/29273726/%C3%AE-subunit-containing-gabaa-receptors-modulate-respiratory-networks
#17
Gaspard Montandon, Haiying Wu, Hattie Liu, Michael T Vu, Beverley A Orser, Richard L Horner
Persistent and stable respiratory activity across behavioral states is key to homeostasis. Extrasynaptic δ-subunit containing GABAA receptors (δGABAARs) mediate tonic inhibition and regulate network activity. However, the influence of δGABAARs on respiratory rhythm and motor outputs is unknown. We manipulated extra-synaptic GABAA receptor function in the preBötzinger Complex (preBötC), a site central to the generation of inspiratory motor activity in mammals. Activation of preBötC δGABAARs in anesthetized rats and wild-type mice decreased breathing rate...
December 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29273603/tenuous-inhibitory-gabaergic-signaling-in-the-reticular-thalamus
#18
Peter M Klein, Adam Lu, Megan E Harper, Hannah M McKown, Jessica Morgan, Mark P Beenhakker
Maintenance of a low intracellular Cl- concentration ([Cl-]i) is critical for enabling inhibitory neuronal responses to GABAA receptor-mediated signaling. Cl- transporters, including KCC2, and extracellular impermeant anions ([A]o) of the extracellular matrix are both proposed to be important regulators of [Cl-]i Neurons of the reticular thalamic (RT) nucleus express reduced levels of KCC2, indicating that GABAergic signaling may produce excitation in RT neurons. However, by performing perforated patch recordings and calcium imaging experiments in rats (male and female), we find that [Cl-]i remains relatively low in RT neurons...
December 22, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29259544/dichotomous-effects-of-mu-opioid-receptor-activation-on-striatal-low-threshold-spike-interneurons
#19
Rasha Elghaba, Enrico Bracci
Striatal low-threshold spike interneurons (LTSIs) are tonically active neurons that express GABA and nitric oxide synthase and are involved in information processing as well as neurovascular coupling. While mu opioid receptors (MORs) and their ligand encephalin are prominent in the striatum, their action on LTSIs has not been investigated. We addressed this issue carrying out whole-cell recordings in transgenic mice in which the NPY-expressing neurons are marked with green fluorescent protein (GFP). The MOR agonist (D-Ala(2), N-MePhe(4), Gly-ol)-enkephalin (DAMGO) produced dual effects on subpopulations of LTSIs...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29259493/gamma-aminobutyric-acida-receptor-agonist-muscimol-increases-kiss-1-gene-expression-in-hypothalamic-cell-models
#20
Haruhiko Kanasaki, Tuvshintugs Tumurbaatar, Aki Oride, Tomomi Hara, Hiroe Okada, Satoru Kyo
Purpose: Accumulating evidence indicates that hypothalamic kisspeptin plays a pivotal role in the regulation of the hypothalamic-pituitary-gonadal (HPG) axis. In this study, the direct action of the gamma-aminobutyric acid (GABA)A receptor agonist on kisspeptin-expressing neuronal cells was examined. Methods: A hypothalamic cell model of rat hypothalamic cell line R8 (rHypoE8) cells and primary cultures of neuronal cells from fetal rat brains were stimulated with a potent and selective GABAA receptor agonist, muscimol, to determine the expression of the KiSS-1 gene...
October 2017: Reproductive Medicine and Biology
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