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https://www.readbyqxmd.com/read/29169227/korean-red-ginseng-excitation-of-paraventricular-nucleus-neurons-via-non-nmda-glutamate-receptor-activation-in-mice
#1
Yiming Shen, Janardhan P Bhattarai, Soo Joung Park, Gyu Seung Lee, Pan Dong Ryu, Seong Kyu Han
It has been reported that Korean red ginseng (KRG) as a valuable and important traditional medicine has various effects on central nervous system suggesting its complicated actions. Paraventricular nucleus (PVN) neurons of hypothalamus play a critical role for stress responses and hormone secretions. Although many studies have reported the action mechanisms of KRG on various cell and systems, the direct membrane effects of KRG on the PVN neurons which are involved in stress response are still poorly understood...
November 23, 2017: Journal of Veterinary Science
https://www.readbyqxmd.com/read/29168593/respiratory-regulation-by-steroids-in-newborn-rats-a-sex-specific-balance-between-allopregnanolone-and-progesterone-receptors
#2
Vincent Joseph, NagaPraveena Uppari, Hayet Kouchi, Celia De Bruyn, Ryma Boukari, Aida Bairam
We tested the hypothesis that the effects of progesterone on apnoea frequency in newborn rats are the result of a balance between its neuroactive metabolite allopregnanolone (GABAa receptor modulator) and progesterone receptors. We used male and female rats between 10 and 12 days of age and recorded respiratory and metabolic parameters (whole-body plethysmography), and assessed the frequency and duration of apnoeas under normoxia. We tested the effects of a single injection of progesterone (4 mg kg(-1) , i...
November 23, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/29168008/gabaa-receptor-subunit-deregulation-in-the-hippocampus-of-human-foetuses-with-down-syndrome
#3
Ivan Milenkovic, Tamara Stojanovic, Eleonora Aronica, Livia Fülöp, Zsolt Bozsó, Zoltán Máté, Yuchio Yanagawa, Homa Adle-Biassette, Gert Lubec, Gábor Szabó, Tibor Harkany, Gábor G Kovács, Erik Keimpema
The function, regulation and cellular distribution of GABAA receptor subunits have been extensively documented in the adult rodent brain and are linked to numerous neurological disorders. However, there is a surprising lack of knowledge on the cellular (sub-) distribution of GABAA receptor subunits and of their expressional regulation in developing healthy and diseased foetal human brains. To propose a role for GABAA receptor subunits in neurodevelopmental disorders, we studied the developing hippocampus of normal and Down syndrome foetuses...
November 22, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/29167327/learning-induced-modulation-of-the-effect-of-endocannabinoids-on-inhibitory-synaptic-transmission
#4
Sourav Ghosh, Iris Reuveni, Samaa Zidan, Raphael Lamprecht, Edi Barkai
Endocannabinoids are key modulators that regulate central brain functions and behaviours, including learning and memory. At the cellular and molecular levels, endocannabinoids are potent modulators of excitatory and inhibitory synaptic function. Most effects of cannabinoids are thought to be mediated via G protein-coupled cannabinoids receptors. In particular, cannabinoids released from post-synaptic neurons are suggested to act as retrograde messengers, activating presynaptic Type-1 Cannabinoid receptors (CB1R), thereby inducing suppression of synaptic release...
November 22, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/29167323/prefrontal-cortical-specific-differences-in-behavior-and-synaptic-plasticity-between-adolescent-and-adult-mice
#5
Xanthippi Konstantoudaki, Kleanthi Chalkiadaki, Elisavet Vasileiou, Katerina Kalemaki, Domna Karagogeos, Kyriaki Sidiropoulou
Adolescence is a highly vulnerable period for the emergence of major neuropsychological disorders and is characterized by decreased cognitive control and increased risk-taking behavior and novelty seeking. The prefrontal cortex (PFC) is involved in the cognitive control of impulsive and risky behavior. Although the PFC is known to reach maturation later than other cortical areas, little information is available regarding the functional changes from adolescence to adulthood in PFC , particularly compared to other primary cortical areas...
November 22, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/29167116/medullary-raphe-nuclei-activate-the-lumbosacral-defecation-center-through-the-descending-serotonergic-pathway-to-regulate-colorectal-motility-in-rats
#6
Hiroyuki Nakamori, Kiyotada Naitou, Yuuki Horii, Hiroki Shimaoka, Kazuhiro Horii, Hiroki Sakai, Akihiro Yamada, Hidemasa Furue, Takahiko Shiina, Yasutake Shimizu
Colorectal motility is regulated by two defecation centers located in the brain and spinal cord. In previous studies, we have shown that administration of serotonin into the lumbosacral spinal cord causes enhancement of colorectal motility. Since spinal serotonin is derived from neurons of the medullary raphe nuclei including the raphe magnus, raphe obscurus and raphe pallidus, we examined whether stimulation of the medullary raphe nuclei enhances colorectal motility via the lumbosacral defecation center. Colorectal pressure was recorded with a balloon in vivo in anesthetized rats...
November 22, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29164431/response-of-the-gabaergic-system-to-axotomy-of-the-rat-facial-nerve
#7
Reika Kikuchi, Makoto Hamanoue, Maasa Koshimoto, Shinichi Kohsaka, Kazuyuki Nakajima
The responses of inhibitory neurons/synapses to motoneuron injury in the cranial nervous system remain to be elucidated. In this study, we analyzed GABAA receptor (GABAAR) and GABAergic neurons at the protein level in the transected rat facial nucleus. Immunoblotting revealed that the GABAARα1 protein levels in the axotomized facial nucleus decreased significantly 5-14 days post-insult, and these levels remained low for 5 weeks. Immunohistochemical analysis indicated that the GABAARα1-expressing cells were motoneurons...
November 21, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/29163035/npas2-regulation-of-anxiety-like-behavior-and-gabaa-receptors
#8
Angela R Ozburn, Joseph Kern, Puja K Parekh, Ryan W Logan, Zheng Liu, Edgardo Falcon, Darius Becker-Krail, Kush Purohit, Nicole M Edgar, Yanhua Huang, Colleen A McClung
Abnormal circadian rhythms and circadian genes are strongly associated with several psychiatric disorders. Neuronal PAS Domain Protein 2 (NPAS2) is a core component of the molecular clock that acts as a transcription factor and is highly expressed in reward- and stress-related brain regions such as the striatum. However, the mechanism by which NPAS2 is involved in mood-related behaviors is still unclear. We measured anxiety-like behaviors in mice with a global null mutation in Npas2 (Npas2 null mutant mice) and found that Npas2 null mutant mice exhibit less anxiety-like behavior than their wild-type (WT) littermates (in elevated plus maze, light/dark box and open field assay)...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29162865/gaba-a-receptor-coupling-junction-and-pore-gabrb3-mutations-are-linked-to-early-onset-epileptic-encephalopathy
#9
Ciria C Hernandez, Yujia Zhang, Ningning Hu, Dingding Shen, Wangzhen Shen, Xiaoyan Liu, Weijing Kong, Yuwu Jiang, Robert L Macdonald
GABAA receptors are brain inhibitory chloride ion channels. Here we show functional analyses and structural simulations for three de novo missense mutations in the GABAA receptor β3 subunit gene (GABRB3) identified in patients with early-onset epileptic encephalopathy (EOEE) and profound developmental delay. We sought to obtain insights into the molecular mechanisms that might link defects in GABAA receptor biophysics and biogenesis to patients with EOEE. The mutant residues are part of conserved structural domains such as the Cys-loop (L170R) and M2-M3 loop (A305V) that form the GABA binding/channel gating coupling junction and the channel pore (T288N), which are functionally coupled during receptor activation...
November 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29162430/spontaneous-activity-singly-bound-states-and-the-impact-of-alpha1phe64-mutation-on-gabaar-gating-in-the-novel-kinetic-model-based-on-the-single-channel-recordings
#10
Magdalena Kisiel, Magdalena Jatczak, Marek Brodzki, Jerzy W Mozrzymas
GABAA receptor is the primary mediator of inhibition in the adult mammalian brain. Our recent studies revealed that a classic gating scheme for GABAAR needed to be updated with an intermediate step (flipping) and that the α1Phe64 mutation at the GABA binding site affects this transition. However, description of flipping at the single-channel level remains incomplete. In particular, its role in singly-bound and spontaneous activity remains unknown. We have performed thus single-channel recordings over wide range of agonist concentration for wild-type α1β2γ2L receptors and α1Phe64 mutants...
November 18, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29161398/role-of-gabaa-receptor-subtypes-in-the-behavioural-effects-of-intravenous-general-anaesthetics
#11
C J Weir, S J Mitchell, J J Lambert
Since the introduction of general anaesthetics into clinical practice, researchers have been mystified as to how these chemically disparate drugs act to produce their dramatic effects on central nervous system function and behaviour. Scientific advances, particularly during the last 25 years, have now begun to reveal the molecular mechanisms underpinning their behavioural effects. For certain i.v. general anaesthetics, such as etomidate and propofol, a persuasive case can now be made that the GABAA receptor, a major inhibitory receptor in the mammalian central nervous system, is an important target...
December 1, 2017: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/29161354/p140cap-regulates-gabaergic-synaptogenesis-and-development-of-hippocampal-inhibitory-circuits
#12
Isabella Russo, Daniela Gavello, Elisabetta Menna, David Vandael, Carola Veglia, Noemi Morello, Irene Corradini, Elisa Focchi, Annalisa Alfieri, Costanza Angelini, Federico Tommaso Bianchi, Alessandro Morellato, Andrea Marcantoni, Marco Sassoè-Pognetto, Matteo Maria Ottaviani, Latefa Yekhlef, Maurizio Giustetto, Stefano Taverna, Valentina Carabelli, Michela Matteoli, Emilio Carbone, Emilia Turco, Paola Defilippi
The neuronal scaffold protein p140Cap was investigated during hippocampal network formation. p140Cap is present in presynaptic GABAergic terminals and its genetic depletion results in a marked alteration of inhibitory synaptic activity. p140Cap-/- cultured neurons display higher frequency of miniature inhibitory postsynaptic currents (mIPSCs) with no changes of their mean amplitude. Consistent with a potential presynaptic alteration of basal GABA release, p140Cap-/- neurons exhibit a larger synaptic vesicle readily releasable pool, without any variation of single GABAA receptor unitary currents and number of postsynaptic channels...
November 17, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29156239/examining-the-effects-of-alcohol-on-gabaa-receptor-mrna-expression-and-function-in-neural-cultures-generated-from-control-and-alcohol-dependent-donor-induced-pluripotent-stem-cells
#13
Richard Lieberman, Henry R Kranzler, Eric S Levine, Jonathan Covault
Factors influencing the development of alcohol-use disorder (AUD) are complex and heterogeneous. While animal models have been crucial to identifying actions of alcohol on neural cells, human-derived in vitro systems that reflect an individual's genetic background hold promise in furthering our understanding of the molecular and functional effects of alcohol exposure and the pathophysiology of AUD. In this report, we utilized induced pluripotent stem cell (iPSCs)-derived neural cell cultures obtained from healthy individuals (CTLs) and those with alcohol dependence (ADs) to 1) examine the effect of 21-day alcohol exposure on mRNA expression of three genes encoding GABAA receptor subunits (GABRA1, GABRG2, and GABRD) using quantitative PCR, and 2) examine the effect of acute and chronic alcohol exposure on GABA-evoked currents using whole-cell patch-clamp electrophysiology...
August 12, 2017: Alcohol
https://www.readbyqxmd.com/read/29155768/slice-patch-clamp-technique-for-analyzing-learning-induced-plasticity
#14
Hiroyuki Kida, Yuya Sakimoto, Dai Mitsushima
The slice patch clamp technique is a powerful tool for investigating learning-induced neural plasticity in specific brain regions. To analyze motor-learning induced plasticity, we trained rats using an accelerated rotor rod task. Rats performed the task 10 times at 30-s intervals for 1 or 2 days. Performance was significantly improved on the training days compared to the first trial. We then prepared acute brain slices of the primary motor cortex (M1) in untrained and trained rats. Current-clamp analysis showed dynamic changes in resting membrane potential, spike threshold, afterhyperpolarization, and membrane resistance in layer II/III pyramidal neurons...
November 11, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29155148/functional-properties-and-mechanism-of-action-of-pptq-an-allosteric-agonist-and-low-nanomolar-positive-allosteric-modulator-at-gabaa-receptors
#15
Nawid Madjroh, Emma Rie Olander, Christoffer Bundgaard, Pella Cecilia Söderhielm, Anders A Jensen
The former sedative-hypnotic and recreational drug methaqualone (Quaalude) is a moderately potent, non-selective positive allosteric modulator (PAM) at GABAA receptors (GABAARs) (Hammer et al., 2015). In the present study, we have identified a novel methaqualone analog, 2-phenyl-3-(p-tolyl)quinazolin-4(3H)-one (PPTQ), in a screening of 67 analogs at five αβ2γ2S GABAAR subtypes and delineated its functional properties and mechanism of action at wild-type and mutant GABAARs expressed in Xenopus oocytes by two-electrode voltage clamp electrophysiology...
November 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29150461/gabaa-receptor-activation-in-the-allosteric-coagonist-model-framework-relationship-between-ec50-and-basal-activity
#16
Gustav Akk, Daniel J Shin, Allison L Germann, Joseph H Steinbach
The concerted transition model for multimeric proteins is a simple formulation for analyzing the behavior of transmitter-gated ion channels. Here, we use the model to examine the relationship between the EC50 for activation of the GABAA receptor by the transmitter GABA and basal activity employing concatemeric ternary GABAA receptors expressed in Xenopus oocytes. The basal activity reflects receptor function in the absence of transmitter, and can be changed either by mutation to increase constitutive activity, or by addition of a second agonist (acting at a different site) to increase background activity...
November 17, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/29146941/developmental-excitatory-to-inhibitory-gaba-polarity-switch-is-disrupted-in-22q11-2-deletion-syndrome-a-potential-target-for-clinical-therapeutics
#17
Hayder Amin, Federica Marinaro, Davide De Pietri Tonelli, Luca Berdondini
Individuals with 22q11.2 microdeletion syndrome (22q11.2 DS) show cognitive and behavioral dysfunctions, developmental delays in childhood and risk of developing schizophrenia and autism. Despite extensive previous studies in adult animal models, a possible embryonic root of this syndrome has not been determined. Here, in neurons from a 22q11.2 DS mouse model (Lgdel (+/-)), we found embryonic-premature alterations in the neuronal chloride cotransporters indicated by dysregulated NKCC1 and KCC2 protein expression levels...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29146239/innately-activated-tlr4-signal-in-the-nucleus-accumbens-is-sustained-by-crf-amplification-loop-and-regulates-impulsivity
#18
Irina Balan, Kaitlin T Warnock, Adam Puche, Marjorie C Gondre-Lewis, Laure Aurelian
Cognitive impulsivity is a heritable trait believed to represent the behavior that defines the volition to initiate alcohol drinking. We have previously shown that a neuronal Toll-like receptor 4 (TLR4) signal located in the central amygdala (CeA) and ventral tegmental area (VTA) controls the initiation of binge drinking in alcohol-preferring P rats, and TLR4 expression is upregulated by alcohol-induced corticotropin-releasing factor (CRF) at these sites. However, the function of the TLR4 signal in the nucleus accumbens shell (NAc-shell), a site implicated in the control of reward, drug-seeking behavior and impulsivity and the contribution of other signal-associated genes, are still poorly understood...
November 13, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29143219/glutamatergic-gabaergic-and-endocannabinoid-neurotransmissions-within-the-dorsal-hippocampus-modulate-the-cardiac-baroreflex-function-in-rats
#19
Nilson Carlos Ferreira-Junior, Davi Campos Lagatta, Leonardo Barbosa Moraes Resstel
The dorsal hippocampus (DH) is involved in the modulation of the cardiac baroreflex function. There is a wide expression of the NMDA and AMPA/Kainate receptors within the DH. Glutamate administration into the DH triggers both tachycardia and pressor responses. Moreover, GABAergic interneurons and endocannabinoid system play an important role in modulation of the activity of glutamatergic neurons within the DH. Therefore, the present work aimed to evaluate the involvement of the glutamatergic, GABAergic, and endocannabinoid neurotransmissions within the DH in cardiac baroreflex function in rats...
November 15, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29143124/the-effect-of-inhibition-on-stimulus-specific-adaptation-in-the-inferior-colliculus
#20
Yaneri A Ayala, Manuel S Malmierca
The inferior colliculus is a center of convergence for inhibitory and excitatory synaptic inputs that may be activated simultaneously by sound stimulation. Stimulus repetition may generate response habituation by changing the efficacy of neuron's synaptic inputs. Specialized IC neurons reduce their response to repetitive tones, but restore their firing when a different and infrequent tone occurs, a phenomenon known as stimulus specific adaptation. Here, using the microiontophoresis technique, we determined the role of GABAA-, GABAB-, and glycinergic receptors in stimulus-specific adaptation (SSA)...
November 15, 2017: Brain Structure & Function
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