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https://www.readbyqxmd.com/read/29218745/expression-of-the-potassium-chloride-co-transporter-kcc2-within-the-avian-song-system
#1
Christopher E Vaaga, Kimberly E Miller, Agnes L Bodor, David J Perkel
Songbirds learn to produce vocalizations early in life by listening to, then copying the songs of conspecific males. The anterior forebrain pathway, homologous to a basal ganglia-forebrain circuit, is essential for song learning. The projection between the striato-pallidal structure, Area X, and the medial portion of the dorsolateral thalamic nucleus (DLM) is strongly hyperpolarizing in adults, due to a very negative chloride reversal potential (Person and Perkel, 2005). The chloride reversal potential is determined, in part, by the expression level of a neuron-specific potassium-chloride cotransporter, KCC2, which is developmentally upregulated in mammals...
December 8, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/29216044/reply-to-the-small-molecule-clp257-does-not-modify-activity-of-the-k-cl-co-transporter-kcc2-but-does-potentiate-gabaa-receptor-activity
#2
Martin Gagnon, Marc J Bergeron, Jimena Perez-Sanchez, Isabel Plasencia-Fernández, Louis-Etienne Lorenzo, Antoine G Godin, Annie Castonguay, Robert P Bonin, Yves De Koninck
No abstract text is available yet for this article.
December 7, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29216042/the-small-molecule-clp257-does-not-modify-activity-of-the-k-cl-co-transporter-kcc2-but-does-potentiate-gabaa-receptor-activity
#3
Ross A Cardarelli, Karen Jones, Lucie I Pisella, Heike J Wobst, Lisa J McWilliams, Paul M Sharpe, Matthew P Burnham, David J Baker, Ilona Chudotvorova, Justine Guyot, Liliya Silayeva, Danielle H Morrow, Niek Dekker, Stephen Zicha, Paul A Davies, Jörg Holenz, Mark E Duggan, John Dunlop, Robert J Mather, Qi Wang, Igor Medina, Nicholas J Brandon, Tarek Z Deeb, Stephen J Moss
No abstract text is available yet for this article.
December 7, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29212780/excitatory-gabaergic-action-and-increased-vasopressin-synthesis-in-hypothalamic-magnocellular-neurosecretory-cells-underlie-the-high-plasma-level-of-vasopressin-in-diabetic-rat
#4
Young-Beom Kim, Woong Bin Kim, Won Woo Jung, Xiangyan Jin, Yoon Sik Kim, Byoungjae Kim, Hee Chul Han, Gene D Block, Christopher S Colwell, Yang In Kim
Diabetes mellitus (DM) is associated with increased plasma levels of arginine-vasopressin (AVP) which may aggravate hyperglycemia and nephropathy. However, the mechanisms by which DM may cause the increased AVP levels are not known. Electrophysiological recordings in the supraoptic nucleus (SON) slices from streptozotocin-induced DM model (STZ) rats and vehicle-treated control rats revealed that GABA functions generally as an excitatory neurotransmitter in the AVP neurons of STZ rats, whereas it evoked usually inhibitory responses in the cells of control animals...
December 6, 2017: Diabetes
https://www.readbyqxmd.com/read/29197650/kcc2-epileptiform-synchronization-and-epileptic-disorders
#5
REVIEW
Graziella Di Cristo, Patricia N Awad, Shabnam Hamidi, Massimo Avoli
The K+-Cl- co-transporter KCC2 is a neuron-specific, Cl- extruder that uses K+ gradient for maintaining low intracellular [Cl-]. It is indeed well established that sustaining an outwardly-directed electrochemical Cl- gradient across the neuronal membrane is fundamental for a proper function of postsynaptic GABAA receptor signaling. In particular, studies in the last two decades have shown that KCC2 activity is important to maintain a hyperpolarizing GABAergic neurotransmission. Conversely, low KCC2 activity should lead to depolarizing, and under specific conditions, excitatory GABAergic transmission...
November 29, 2017: Progress in Neurobiology
https://www.readbyqxmd.com/read/29184062/molecular-architecture-of-potassium-chloride-co-transporter-kcc2
#6
Morgane Agez, Patrick Schultz, Igor Medina, David J Baker, Matthew P Burnham, Ross A Cardarelli, Leslie C Conway, Kelly Garnier, Stefan Geschwindner, Anders Gunnarsson, Eileen J McCall, Alexandre Frechard, Stéphane Audebert, Tarek Z Deeb, Stephen J Moss, Nicholas J Brandon, Qi Wang, Niek Dekker, Anass Jawhari
KCC2 is a neuron specific K+-Cl- co-transporter that controls neuronal chloride homeostasis, and is critically involved in many neurological diseases including brain trauma, epilepsies, autism and schizophrenia. Despite significant accumulating data on the biology and electrophysiological properties of KCC2, structure-function relationships remain poorly understood. Here we used calixarene detergent to solubilize and purify wild-type non-aggregated and homogenous KCC2. Specific binding of inhibitor compound VU0463271 was demonstrated using surface plasmon resonance (SPR)...
November 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29176664/gabaa-receptor-dependent-synaptic-inhibition-rapidly-tunes-kcc2-activity-via-the-cl-sensitive-wnk1-kinase
#7
Martin Heubl, Jinwei Zhang, Jessica C Pressey, Sana Al Awabdh, Marianne Renner, Ferran Gomez-Castro, Imane Moutkine, Emmanuel Eugène, Marion Russeau, Kristopher T Kahle, Jean Christophe Poncer, Sabine Lévi
The K+-Cl- co-transporter KCC2 (SLC12A5) tunes the efficacy of GABAA receptor-mediated transmission by regulating the intraneuronal chloride concentration [Cl-]i. KCC2 undergoes activity-dependent regulation in both physiological and pathological conditions. The regulation of KCC2 by synaptic excitation is well documented; however, whether the transporter is regulated by synaptic inhibition is unknown. Here we report a mechanism of KCC2 regulation by GABAA receptor (GABAAR)-mediated transmission in mature hippocampal neurons...
November 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/29174921/embryonic-development-of-gabaergic-terminals-in-the-mouse-hypothalamic-nuclei-involved-in-feeding-behavior
#8
Masato Kobayashi, Chigusa Shimizu-Okabe, Jeongtae Kim, Shiori Kobayashi, Masayuki Matsushita, Hiroaki Masuzaki, Chitoshi Takayama
The inhibitory neurotransmitter gamma-amino butyric acid (GABA) plays important roles in energy balance and feeding behavior in the hypothalamus. To reveal the time course of GABAergic network formation, we examined the immunohistochemical localization of glutamic acid decarboxylase (GAD), a GABAergic neuron marker, vesicular GABA transporter (VGAT), a marker of inhibitory terminals, and K+-Cl--cotransporter2 (KCC2), which shifts GABA action from excitation to inhibition, in the developing mouse hypothalamus...
November 21, 2017: Neuroscience Research
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
#9
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/29146047/maternal-immune-activation-delays-excitatory-to-inhibitory-gamma-aminobutyric-acid-switch-in-offspring
#10
Irene Corradini, Elisa Focchi, Marco Rasile, Raffaella Morini, Genni Desiato, Romana Tomasoni, Michela Lizier, Elsa Ghirardini, Riccardo Fesce, Diego Morone, Isabella Barajon, Flavia Antonucci, Davide Pozzi, Michela Matteoli
BACKGROUND: The association between maternal infection and neurodevelopmental defects in progeny is well established, although the biological mechanisms and the pathogenic trajectories involved have not been defined. METHODS: Pregnant dams were injected intraperitoneally at gestational day 9 with polyinosinic:polycytidylic acid. Neuronal development was assessed by means of electrophysiological, optical, and biochemical analyses. RESULTS: Prenatal exposure to polyinosinic:polycytidylic acid causes an imbalanced expression of the Na+-K+-2Cl- cotransporter 1 and the K+-Cl- cotransporter 2 (KCC2)...
November 14, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29143559/k-cl-co-transporter-2-kcc2-a-membrane-trafficking-perspective
#11
Bor Luen Tang
K(+)-Cl(-) co-transporter 2 (KCC2/SLC12A5) is a neuronal specific cation chloride co-transporter which is active under isotonic conditions, and thus a key regulator of intracellular Cl(-) levels. It also has an ion transporter-independent structural role in modulating the maturation and regulation of excitatory glutamatergic synapses. KCC2 levels are developmentally regulated, and a postnatal upregulation of KCC2 generates a low intracellular chloride concentration that allows the neurotransmitters γ-aminobutyric acid (GABA) and glycine to exert inhibitory neurotransmission through its Cl(-) permeating channel...
November 16, 2017: Molecular Membrane Biology
https://www.readbyqxmd.com/read/29113945/changes-in-the-expression-and-localization-of-signaling-molecules-in-mouse-facial-motor-neurons-during-regeneration-of-facial-nerves
#12
Jeongtae Kim, Shiori Kobayashi, Chigusa Shimizu-Okabe, Akihito Okabe, Changjong Moon, Taekyun Shin, Chitoshi Takayama
After injury, peripheral axons usually re-extend toward their target, and neuronal functions recover. Previous studies have reported that expression of various molecules are transiently altered in motor neurons after nerve injury, but the time course of these changes and their relationship with functional recovery have not been clearly demonstrated. We used the mouse facial nerve transection and suturing model, and examined the changes in expression of five molecules, choline acetyl transferase (ChAT), galanin, calcitonin gene-related protein (CGRP), gephyrin, and potassium chloride co-transporter 2 (KCC2) in the facial motor neurons after surgery until recovery...
November 4, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/29092909/n-ethylmaleimide-increases-kcc2-activity-by-modulating-transporter-phosphorylation
#13
Leslie C Conway, Ross A Cardarelli, Yvonne E Moore, Karen Jones, Lisa J McWilliams, David J Baker, Matthew P Burnham, Roland W Bürli, Qi Wang, Nicholas J Brandon, Stephen J Moss, Tarek Z Deeb
The K+/Cl- co-transporter (KCC2) is selectively expressed in the adult nervous system, and allows neurons to maintain low intracellular Cl- levels. Thus, KCC2 activity is an essential prerequisite for fast hyperpolarizing synaptic inhibition mediated by type A γ-aminobutyric acid receptors (GABAA), which are Cl- permeable, ligand-gated ion channels. Consistent with this, deficits in the activity of KCC2 lead to epilepsy, and are also implicated in neurodevelopmental disorders, neuropathic pain, and schizophrenia...
November 1, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29058295/effects-of-high-frequency-repetitive-transcranial-magnetic-stimulation-on-kcc2-expression-in-rats-with-spasticity-following-spinal-cord-injury
#14
Wei Gao, Li-Guo Yu, Ya-Li Liu, Mo Chen, Yi-Zhao Wang, Xiao-Lin Huang
The effect of high-frequency repetitive transcranial magnetic stimulation (rTMS) on potassium- chloride cotransporter-2 (KCC2) protein expression following spinal cord injury (SCI) and the action mechanism were investigated. SCI models were established in SD rats. Five groups were set up randomly: normal control group, SCI 7-day (7D) model group, SCI 14-day (14D) model group, SCI-7D rTMS group and SCI-14D rTMS group (n=5 each). The rats in SCI rTMS groups were treated with 10 Hz rTMS from 8th day and 15th day after SCI respectively, once every day, 5 days every week, a total of 4 weeks...
October 2017: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/29045814/role-of-kcc2-dependent-potassium-efflux-in-4-aminopyridine-induced-epileptiform-synchronization
#15
Oscar C González, Zahra Shiri, Giri P Krishnan, Timothy L Myers, Sylvain Williams, Massimo Avoli, Maxim Bazhenov
A balance between excitation and inhibition is necessary to maintain stable brain network dynamics. Traditionally, seizure activity is believed to arise from the breakdown of this delicate balance in favor of excitation with loss of inhibition. Surprisingly, recent experimental evidence suggests that this conventional view may be limited, and that inhibition plays a prominent role in the development of epileptiform synchronization. Here, we explored the role of the KCC2 co-transporter in the onset of inhibitory network-induced seizures...
October 16, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/29035834/synergistic-effect-of-mild-hypothermia-and-the-notch-inhibitor-dapt-against-post-stroke-seizures
#16
Guo-Shuai Yang, Xiao-Yan Zhou, Xue-Fang An, Xuan-Jun Liu, Yan-Jun Zhang, Dan Yu
Seizure is a serious complication of stroke, indicating poor prognosis. Notch signaling is associated with neuronal activity. Inhibition of Notch signaling suppresses seizure activity induced by kainic acid. The present study investigated the effect of the Notch inhibitor, DAPT, alone or in combination with mild hypothermia, on post-stroke seizures. A global cerebral ischemia (GCI) model was performed in Sprague Dawley (SD) male rats. Seizure activity was evaluated by the frequency of seizure attacks, seizure severity scores, and seizure discharges...
October 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29028184/native-kcc2-interactome-reveals-pacsin1-as-a-critical-regulator-of-synaptic-inhibition
#17
Vivek Mahadevan, C Sahara Khademullah, Zahra Dargaei, Jonah Chevrier, Pavel Uvarov, Julian Kwan, Richard D Bagshaw, Tony Pawson, Andrew Emili, Yves De Koninck, Victor Anggono, Matti Airaksinen, Melanie A Woodin
KCC2 is a neuron-specific K(+)-Cl(-) cotransporter essential for establishing the Cl(-) gradient required for hyperpolarizing inhibition in the central nervous system (CNS). KCC2 is highly localized to excitatory synapses where it regulates spine morphogenesis and AMPA receptor confinement. Aberrant KCC2 function contributes to human neurological disorders including epilepsy and neuropathic pain. Using functional proteomics, we identified the KCC2-interactome in the mouse brain to determine KCC2-protein interactions that regulate KCC2 function...
October 13, 2017: ELife
https://www.readbyqxmd.com/read/28990565/-calpain-as-a-new-therapeutic-target-for-treating-spasticity-after-a-spinal-cord-injury
#18
Vanessa Plantier, Frédéric Brocard
After a spinal cord injury (SCI), patients develop spasticity, a motor disorder characterized by hyperreflexia and stiffness of muscles. Spasticity results from alterations in motoneurons with an upregulation of their persistent sodium current (I NaP), simultaneously with a disinhibition caused by a reduction of expression of chloride (Cl(-)) co-transporters KCC2. Until recently the origin of alterations was unknown. After reviewing pathophysiology of spasticity, the manuscript relates our recent work showing a tight relationship between the calpain-dependent proteolysis of voltage-gated sodium channels, the upregulation of I NaP and spasticity following SCI...
June 2017: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/28982596/subsequent-maternal-separation-exacerbates-neurobehavioral-abnormalities-in-rats-neonatally-exposed-to-sevoflurane-anesthesia
#19
Jiaojiao Yang, Lingsha Ju, Min Jia, Hui Zhang, Xiaoru Sun, Muhuo Ji, Jianjun Yang, Anatoly E Martynyuk
Several recent studies suggest that in the human population, a routine, short anesthetic in otherwise healthy infants is void of neurodevelopmental insult. On the other hand, many human retrospective epidemiological studies report evidence of cognitive abnormalities in children after testing those who had different anesthesia-requiring procedures in early childhood. We tested in a rat model whether post-anesthesia stressful environmental factors can contribute to developmental abnormalities that were initiated by a relatively short exposure to sevoflurane, the most widely used anesthetic in pediatric anesthesia, whose polyvalent actions include enhancement of gamma-aminobutyric acid type A receptor (GABAAR) activity...
November 20, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28973889/simultaneous-two-photon-imaging-of-intracellular-chloride-concentration-and-ph-in-mouse-pyramidal-neurons-in-vivo
#20
Sebastian Sulis Sato, Pietro Artoni, Silvia Landi, Olga Cozzolino, Riccardo Parra, Enrico Pracucci, Francesco Trovato, Joanna Szczurkowska, Stefano Luin, Daniele Arosio, Fabio Beltram, Laura Cancedda, Kai Kaila, Gian Michele Ratto
Intracellular chloride ([Cl(-)]i) and pH (pHi) are fundamental regulators of neuronal excitability. They exert wide-ranging effects on synaptic signaling and plasticity and on development and disorders of the brain. The ideal technique to elucidate the underlying ionic mechanisms is quantitative and combined two-photon imaging of [Cl(-)]i and pHi, but this has never been performed at the cellular level in vivo. Here, by using a genetically encoded fluorescent sensor that includes a spectroscopic reference (an element insensitive to Cl(-) and pH), we show that ratiometric imaging is strongly affected by the optical properties of the brain...
October 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
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