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https://www.readbyqxmd.com/read/29351468/gabaergic-contribution-to-the-muscle-mechanoreflex-mediated-heart-rate-responses-at-the-onset-of-exercise-in-humans
#1
André L Teixeira, Plinio Santos Ramos, Milena Samora, Jeann L Sabino-Carvalho, Djalma Rabelo Ricardo, Eduardo Colombari, Lauro C Vianna
Previous studies indicated that central GABAergic mechanisms are involved in the heart rate (HR) responses at the onset of exercise. Based on previous research that showed similar increases in HR during passive and active cycling, we reasoned that the GABAergic mechanisms involved in the HR responses at the exercise onset is primarily mediated by muscle mechanoreceptors afferents. Therefore, in this study we sought to determine if central GABA mechanisms are involved in the muscle mechanoreflex-mediated HR responses at the onset of exercise in humans...
December 22, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29349630/developmental-changes-in-serotonergic-modulation-of-gabaergic-synaptic-transmission-and-postsynaptic-gabaa-receptor-composition-in-the-cerebellar-nuclei
#2
Fumihito Saitow, Masatoshi Nagano, Hidenori Suzuki
Outputs from the cerebellar nuclei (CN) are important for generating and controlling movement. The activity of CN neurons is controlled not only by excitatory inputs from mossy and climbing fibers and by γ-aminobutyric acid (GABA)-based inhibitory transmission from Purkinje cells in the cerebellar cortex but is also modulated by inputs from other brain regions, including serotonergic fibers that originate in the dorsal raphe nuclei. We examined the modulatory effects of serotonin (5-HT) on GABAergic synapses during development, using rat cerebellar slices...
January 19, 2018: Cerebellum
https://www.readbyqxmd.com/read/29341457/different-effects-of-dexmedetomidine-and-midazolam-on-the-expression-of-nr2b-and-gabaa-%C3%AE-1-following-peripheral-nerve-injury-in-rats
#3
Jiayu Chen, Hanjun Li, Grewo Lim, Michael F McCabe, Wei Zhao, Yunli Yang, Weiqing Ma, Na Li
Neuropathic pain is a complex, chronic pain condition and the treatment is a major clinical challenge. Recent studies have shown that two FDA approved drugs dexmedetomidine (DEX) and midazolam (MZL), may be useful in treating neuropathic pain, but the mechanism is not fully dementated. Here, we investigated the effects and mechanisms of DEX and MZL treatment in the peripheral nerve injury model. Intramuscular injection with DEX and MZL attenuated the development of mechanical allodynia and thermal hyperalgesia in rats with chronic constriction injury (CCI)...
January 17, 2018: IUBMB Life
https://www.readbyqxmd.com/read/29341327/involvement-of-the-dorsal-hippocampus-in-expression-and-extinction-of-cocaine-induced-conditioned-place-preference
#4
Leah N Hitchcock, K Matthew Lattal
A key aspect of substance abuse is that drug taking often occurs in a specific context. As a consequence, exposure to drug-associated contexts can trigger cravings and relapse, even after long periods of abstinence. Although many studies have demonstrated that the hippocampus is critical for developing and retrieving contextual and spatial memories, comparatively little is known about the role of the hippocampus in acquiring and inhibiting memories involving contexts and drugs of abuse. We examined the effects of hippocampal inactivation on expression of cocaine-induced conditioned place preference (CPP) after initial acquisition or extinction of CPP in C57BL/6 mice...
January 17, 2018: Hippocampus
https://www.readbyqxmd.com/read/29336201/poor-motor-function-recovery-after-spinal-cord-injury-in-anxiety-model-mice-with-phospholipase-c-related-catalytically-inactive-protein-type-1-knockout
#5
Taku Fujita, Gentaro Kumagai, Xizhe Liu, Kanichiro Wada, Toshihiro Tanaka, Hitoshi Kudo, Toru Asari, Tatsuhiro Fukutoku, Ayako Sasaki, Yohshiro Nitobe, Yoshikazu Nikaido, Ken-Ichi Furukawa, Masato Hirata, Takashi Kanematsu, Shinya Ueno, Yasuyuki Ishibashi
Mice with a knockout of phospholipase C (PLC)-related inactive protein type 1 (PRIP1-/- mice) display anxiety-like behavior and altered GABAA-receptor pharmacology. Here we examined associations between anxiety and motor-function recovery in PRIP1-/- mice after a spinal-cord injury (SCI) induced by a moderate contusion injury at the 10th thoracic level. Uninjured PRIP1-/- mice spent less distance than wild-type (WT) mice in the center 25% in an open field test (OFT), indicating anxiety-like behavior. Anxiety behavior increased in both WT and PRIP1-/- mice after SCI...
January 16, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29334986/bridging-pro-inflammatory-signals-synaptic-transmission-and-protection-in-spinal-explants-in-vitro
#6
M Medelin, V Giacco, A Aldinucci, G Castronovo, E Bonechi, A Sibilla, M Tanturli, M Torcia, L Ballerini, F Cozzolino, C Ballerini
Multiple sclerosis is characterized by tissue atrophy involving the brain and the spinal cord, where reactive inflammation contributes to the neurodegenerative processes. Recently, the presence of synapse alterations induced by the inflammatory responses was suggested by experimental and clinical observations, in experimental autoimmune encephalomyelitis mouse model and in patients, respectively. Further knowledge on the interplay between pro-inflammatory agents, neuroglia and synaptic dysfunction is crucial to the design of unconventional protective molecules...
January 15, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29331264/altered-levels-of-the-splicing-factor-muscleblind-modifies-cerebral-cortical-function-in-mouse-models-of-myotonic-dystrophy
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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/29298327/gabaergic-mechanisms-involved-in-the-prepulse-inhibition-of-auditory-evoked-cortical-responses-in-humans
#19
Koji Inui, Nobuyuki Takeuchi, Shunsuke Sugiyama, Eishi Motomura, Makoto Nishihara
Despite their essential roles in signal processing in the brain, the functions of interneurons currently remain unclear in humans. We recently developed a method using the prepulse inhibition of sensory evoked cortical responses for functional measurements of interneurons. When a sensory feature is abruptly changed in a continuous sensory stimulus, change-related cortical responses are recorded using MEG. By inserting a weak change stimulus (prepulse) before the test change stimulus, it is possible to observe the inhibition of the test response...
2018: PloS One
https://www.readbyqxmd.com/read/29289597/hippocampal-gabaa-antagonism-reverses-the-novel-object-recognition-deficit-in-sub-chronic-phencyclidine-treated-rats
#20
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
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