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https://www.readbyqxmd.com/read/28445782/the-immunohistochemical-distribution-of-the-gabaa-receptor-%C3%AE-1-%C3%AE-2-%C3%AE-3-%C3%AE-2-3-and-%C3%AE-2-subunits-in-the-human-thalamus
#1
H J Waldvogel, M Munkle, W van Roon-Mom, H Mohler, R L M Faull
The GABAA receptor is the most abundant inhibitory receptor in the human brain and is assembled from a variety of different subunit subtypes which determines their pharmacology and physiology. To determine which GABAA receptor subunit proteins are found in the human thalamus we investigated the distribution of five major GABAA receptor subunits α1, α2, α3, β2,3 and γ2 using immunohistochemical techniques. The α1-, β2,3- and γ2- subunits which combine to form a benzodiazepine sensitive GABAA receptor showed the most intense levels of staining and were the most common subunits found throughout the human thalamus especially in the ventral and posterior nuclear groups...
April 23, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28445732/the-hect-family-ubiquitin-ligase-eel-1-regulates-neuronal-function-and-development
#2
Karla J Opperman, Ben Mulcahy, Andrew C Giles, Monica G Risley, Rayna L Birnbaum, Erik D Tulgren, Ken Dawson-Scully, Mei Zhen, Brock Grill
Genetic changes in the HECT ubiquitin ligase HUWE1 are associated with intellectual disability, but it remains unknown whether HUWE1 functions in post-mitotic neurons to affect circuit function. Using genetics, pharmacology, and electrophysiology, we show that EEL-1, the HUWE1 ortholog in C. elegans, preferentially regulates GABAergic presynaptic transmission. Decreasing or increasing EEL-1 function alters GABAergic transmission and the excitatory/inhibitory (E/I) balance in the worm motor circuit, which leads to impaired locomotion and increased sensitivity to electroshock...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445715/altered-somatosensory-cortex-neuronal-activity-in-a-rat-model-of-parkinson-s-disease-and-levodopa-induced-dyskinesias
#3
Mesbah Alam, Regina Rumpel, Xingxing Jin, Christof von Wrangel, Sarah Tschirner, Joachim K Krauss, Claudia Grothe, Andreas Ratzka, Kerstin Schwabe
Several findings support the concept that sensorimotor integration is disturbed in Parkinson's disease (PD) and in levodopa-induced dyskinesias. In this study, we explored the neuronal firing activity of excitatory pyramidal cells and inhibitory interneurons in the forelimb region of the primary somatosensory cortex (S1FL-Ctx), along with its interaction with oscillatory activity of the primary motor cortex (MCtx) in 6-hydroxydopamine lesioned hemiparkinsonian (HP) and levodopa-primed dyskinetic (HP-LID) rats as compared to controls under urethane (1...
April 23, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28445465/assembly-of-functionally-integrated-human-forebrain-spheroids
#4
Fikri Birey, Jimena Andersen, Christopher D Makinson, Saiful Islam, Wu Wei, Nina Huber, H Christina Fan, Kimberly R Cordes Metzler, Georgia Panagiotakos, Nicholas Thom, Nancy A O'Rourke, Lars M Steinmetz, Jonathan A Bernstein, Joachim Hallmayer, John R Huguenard, Sergiu P Paşca
The development of the nervous system involves a coordinated succession of events including the migration of GABAergic (γ-aminobutyric-acid-releasing) neurons from ventral to dorsal forebrain and their integration into cortical circuits. However, these interregional interactions have not yet been modelled with human cells. Here we generate three-dimensional spheroids from human pluripotent stem cells that resemble either the dorsal or ventral forebrain and contain cortical glutamatergic or GABAergic neurons...
April 26, 2017: Nature
https://www.readbyqxmd.com/read/28445148/pkc-and-camk-ii-inhibitions-coordinately-rescue-ischemia-induced-gabaergic-neuron-dysfunction
#5
Li Huang, Chun Wang, Shidi Zhao, Rongjing Ge, Sudong Guan, Jin-Hui Wang
Cerebral ischemia leads to neuronal death for stroke, in which the imbalance between glutamatergic neurons and GABAergic neurons toward neural excitotoxicity is presumably involved. GABAergic neurons are vulnerable to pathological factors and impaired in an early stage of ischemia. The rescue of GABAergic neurons is expected to be the strategy to reserve ischemic neuronal impairment. As protein kinase C (PKC) and calmodulin-dependent protein kinase II (CaMK-II) are activated during ischemia, we have investigated whether the inhibitions of these kinases rescue the ischemic impairment of cortical GABAergic neurons...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28443506/catestain-a-master-regulator-of-cardiovascular-functions
#6
Sushil K Mahata, Malapaka Kiranmayi, Nitish R Mahapatra
Cardiovascular disease (CVD), the most common cause of death globally, accounts for ~30% of all deaths worldwide. Hypertension is a common contributor to morbidity and mortality from CVD. The plasma concentration of chromogranin A (CgA) is elevated in patients with CVD as well as patients with established human essential hypertension and heart failure (HF). In contrast, the plasma level of the CgA-derived peptide catestatin (CST) is diminished in human essential hypertension. Low conversion of CgA-to-CST has been associated with increased mortality in patients hospitalized with acute HF...
April 24, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28436626/-the-role-of-central-cholinergic-system-in-epilepsy
#7
Ying Wang, Yi Wang, Zhong Chen
Epilepsy is a chronic neurological disorder, which is not only related to the imbalance between excitatory glutamic neurons and inhibitory GABAergic neurons, but also related to abnormal central cholinergic regulation. This article summarizes the scientific background and experimental data about cholinergic dysfunction in epilepsy from both cellular and network levels, further discusses the exact role of cholinergic system in epilepsy. In the cellular level, several types of epilepsy are believed to be associated with aberrant metabotropic muscarinic receptors in several different brain areas, while the mutations of ionotropic nicotinic receptors have been reported to result in a specific type of epilepsy-autosomal dominant nocturnal frontal lobe epilepsy...
January 25, 2017: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/28432142/structural-similarities-between-neuregulin-1-3-isoforms-determine-their-subcellular-distribution-and-signaling-mode-in-central-neurons
#8
Detlef Vullhorst, Tanveer Ahmad, Irina Karavanova, Carolyn Keating, Andres Buonanno
The Neuregulin (NRG) family of ErbB ligands is comprised of numerous variants originating from the use of different genes, alternative promoters and splice variants. NRGs have generally been thought to be transported to axons and presynaptic terminals where they signal via ErbB3/4 receptors in paracrine or juxtacrine mode. However, we recently demonstrated that unprocessed pro-NRG2 accumulates on cell bodies and proximal dendrites, and that NMDAR activity is required for shedding of its ectodomain by metalloproteinases...
April 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28429899/neurotransmitter-systems-neuroanatomical-pathology-and-cell-death-in-schizophrenia-update-and-perspectives
#9
Hazael Avila-Rojas, Hugo Sandoval-Zamora, Iván Pérez-Neri
Schizophrenia is a thought disorder characterized by delusional thinking which may be accompanied by hallucinations involving any sensory modality. Schizophrenia may be associated with several neurologic and psychiatric disorders. Also, it may be induced by drugs. In spite of the similarity in psychoses symptomatology, it is unknown if it involves the same underlying neurobiologic mechanisms in those cases. Schizophrenic patients exhibit not only neuroanatomical alterations, but also, distortion of several neurotransmitter systems...
June 2016: Investigación Clínica
https://www.readbyqxmd.com/read/28429259/early-morphological-and-functional-changes-in-the-gabaergic-system-of-hippocampus-in-the-rat-lithium-pilocarpine-model-of-epilepsy
#10
V B Karyakin, D S Vasil'ev, I A Zhuravin, A V Zaitsev, L G Magazanik
We studied early alterations in the GABAergic system of the rat hippocampus in the lithium-pilocarpine model of epilepsy. Twenty-four hours after the pilocarpine treatment, a decrease in the number of calretinin-positive interneurons was observed in the CA1 field of the hippocampus, whereas the number of parvalbumin-positive interneurons remained unchanged. The decreased levels of the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD67) and the membrane GABA transporter GAT1 were revealed using Western blot analysis...
January 2017: Doklady Biological Sciences: Proceedings of the Academy of Sciences of the USSR, Biological Sciences Sections
https://www.readbyqxmd.com/read/28427143/activity-induced-spontaneous-spikes-in-gabaergic-neurons-suppress-seizure-discharges-an-implication-of-computational-modeling
#11
Wei Lu, Jing Feng, Bo Wen, Kewei Wang, Jin-Hui Wang
BACKGROUND: Epilepsy, a prevalent neurological disorder, appears self-termination. The endogenous mechanism for seizure self-termination remains to be addressed in order to develop new strategies for epilepsy treatment. We aim to examine the role of activity-induced spontaneous spikes at GABAergic neurons as an endogenous mechanism in the seizure self-termination. METHODS AND RESULTS: Neuronal spikes were induced by depolarization pulses at cortical GABAergic neurons from temporal lobe epilepsy patients and mice, in which some of these neurons fired activity-induced spontaneous spikes...
February 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427019/transplantation-of-inhibitory-precursor-cells-from-medial-ganglionic-eminence-produces-distinct-responses-in-two-different-models-of-acute-seizure-induction
#12
Daisyléa de Souza Paiva, Simone Amaro Alves Romariz, Maria Fernanda Valente, Luiz Bruno Moraes, Luciene Covolan, Maria Elisa Calcagnotto, Beatriz Monteiro Longo
Medial ganglionic eminence (MGE) is one of the sources of inhibitory interneurons during development. Following transplantation in postnatal developing brain, MGE cells can increase local inhibition suggesting a possible protection to GABAergic dysfunction in brain disorders, such as epilepsy. Since it has been shown that MGE-derived cells harvested as neurospheres are able to suppress seizures, it might be important to investigate whether these protective effects would change in different seizure models. Here, we used pentylenetetrazole-(PTZ) and maximal electroshock (MES)-induced seizure models to test whether the transplantation of MGE cells would increase the threshold to trigger acute seizures...
April 17, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28426941/behavioral-deficits-and-neural-damage-of-caenorhabditis-elegans-induced-by-three-rare-earth-elements
#13
Tiantian Xu, Manke Zhang, Jiani Hu, Zihan Li, Taipu Wu, Jianing Bao, Siyu Wu, Lili Lei, Defu He
Rare earth elements (REEs) are widely used in industry, agriculture, medicine and daily life in recent years. However, environmental and health risks of REEs are still poorly understood. In this study, neurotoxicity of trichloride neodymium, praseodymium and scandium were evaluated using nematode Caenorhabditis elegans as the assay system. Median lethal concentrations (48 h) were 99.9, 157.2 and 106.4 mg/L for NdCl3, PrCl3 and ScCl3, respectively. Sublethal dose (10-30 mg/L) of these trichloride salts significantly inhibited body length of nematodes...
April 17, 2017: Chemosphere
https://www.readbyqxmd.com/read/28426550/neuropathic-pain-after-chronic-nerve-constriction-may-not-correlate-with-chloride-dysregulation-in-mouse-trigeminal-nucleus-caudalis-neurons
#14
Alberto Castro, Ying Li, Charles Raver, Ramesh Chandra, Radi Masri, Mary Kay Lobo, Asaf Keller
Changes in chloride reversal potential in rat spinal cord neurons have previously been associated with persistent pain in nerve injury and inflammation models. These changes correlate with a decrease in the expression of the potassium% chloride transporter, KCC2, and with increases in neuronal excitability. Here, we test the hypothesis that similar changes occur in mice with neuropathic pain induced by chronic constriction injury of the trigeminal infraorbital nerve (CCI¬-ION). This model allows us to distinguish an acute pain phase (3-¬5 days after injury) from a persistent pain phase (12¬-14 days after CCI-¬ION)...
April 18, 2017: Pain
https://www.readbyqxmd.com/read/28425097/seizure-frequency-correlates-with-loss-of-dentate-gyrus-gabaergic-neurons-in-a-mouse-model-of-temporal-lobe-epilepsy
#15
Paul S Buckmaster, Emily Abrams, Xiling Wen
Epilepsy occurs in one of 26 people. Temporal lobe epilepsy is common and can be difficult to treat effectively. It can develop after brain injuries that damage the hippocampus. Multiple pathophysiological mechanisms involving the hippocampal dentate gyrus have been proposed. The present study evaluated a mouse model of temporal lobe epilepsy to test which pathological changes in the dentate gyrus correlate with seizure frequency and help prioritize potential mechanisms for further study. FVB mice (n = 127) that had experienced status epilepticus after systemic treatment with pilocarpine 31 - 61 d earlier were video-monitored for spontaneous, convulsive seizures 9 h/d every day for 24 - 36 d...
April 20, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28421533/changes-in-the-prefrontal-glutamatergic-and-parvalbumin-systems-of-mice-exposed-to-unpredictable-chronic-stress
#16
Ryan Shepard, Laurence Coutellier
The prefrontal cortex (PFC) is highly sensitive to the effects of stress, a known risk factor of mood disorders including anxiety and depression. Abnormalities in PFC functioning have been well described in humans displaying stress-induced depressive symptoms, and hypoactivity of the PFC is now recognized to be a key feature of the depressed brain. However, little is known about the causes and mechanisms leading to this altered prefrontal functional activity in the context of stress-related mood disorders. We previously showed that unpredictable chronic mild stress (UCMS) in mice increases prefrontal expression of parvalbumin (PV), an activity-dependent calcium-binding albumin protein expressed in a specific subtype of GABAergic neurons, highlighting a potential mechanism through which chronic stress leads to hypofunction of the PFC...
April 18, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28420711/excitatory-neurons-sculpt-gabaergic-neuronal-connectivity-in-the-c-elegans-motor-circuit
#17
Belinda Barbagallo, Alison Philbrook, Denis Touroutine, Navonil Banerjee, Devyn Oliver, Christopher M Lambert, Michael M Francis
Establishing and maintaining the appropriate number of GABA synapses is key for balancing excitation and inhibition in the nervous system, though we have only a limited understanding of the mechanisms controlling GABA circuit connectivity. Here, we show that disrupting cholinergic innervation of GABAergic neurons in the C. elegans motor circuit alters GABAergic neuron synaptic connectivity. These changes are accompanied by a reduced frequency and increased amplitude of GABAergic synaptic events. Acute genetic disruption in early development-during the integration of post-embryonic born GABAergic neurons into the circuit-produces irreversible effects on GABAergic synaptic connectivity that mimic those produced by chronic manipulations...
April 18, 2017: Development
https://www.readbyqxmd.com/read/28419871/short-term-inhibition-of-gabaergic-ipscs-induced-by-association-of-pre-and-postsynaptic-activation-in-the-neonatal-hippocampus
#18
Megumi Taketo, Hiroko Matsuda
Activity-dependent plasticity including short and long-term depression accompanied by a reduction in transmitter release probability has been demonstrated in both inhibitory and excitatory synapses. In the neonatal hippocampus, repetitive postsynaptic depolarization is followed by presynaptic alterations of the efficacy of GABAAergic transmission. Both facilitation and inhibition have been observed, but the mechanisms underlying this plasticity have not yet been elucidated. In the present experiment, repetitive postsynaptic depolarization by itself did not cause marked alterations of spontaneous inhibitory postsynaptic currents (sIPSCs)...
April 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28419057/gabaergic-modulation-of-noradrenaline-release-caused-by-blood-pressure-changes-in-the-rat-median-preoptic-area
#19
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 20, 2017: Neuroreport
https://www.readbyqxmd.com/read/28418172/analgesic-effect-of-clobazam-in-chronic-low-back-pain-but-not-in-experimentally-induced-pain
#20
J Schliessbach, P H Vuilleumier, A Siegenthaler, L Bütikofer, A Limacher, P Juni, H U Zeilhofer, L Arendt-Nielsen, M Curatolo
BACKGROUND: Chronic pain is frequently associated with hypersensitivity of the nervous system, and drugs that increase central inhibition are therefore a potentially effective treatment. Benzodiazepines are potent modulators of GABAergic neurotransmission and are known to exert antihyperalgesic effects in rodents, but translation into patients are lacking. This study investigates the effect of the benzodiazepine clobazam in chronic low-back pain in humans. The aim of this study is to explore the effect of GABA modulation on chronic low-back pain and on quantitative sensory tests...
April 18, 2017: European Journal of Pain: EJP
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