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https://www.readbyqxmd.com/read/28344592/dysbindin-deficiency-modifies-the-expression-of-gaba-neuron-and-ion-permeation-transcripts-in-the-developing-hippocampus
#1
Jennifer Larimore, Stephanie A Zlatic, Miranda Arnold, Kaela S Singleton, Rebecca Cross, Hannah Rudolph, Martha V Bruegge, Andrea Sweetman, Cecilia Garza, Eli Whisnant, Victor Faundez
The neurodevelopmental factor dysbindin is required for synapse function and GABA interneuron development. Dysbindin protein levels are reduced in the hippocampus of schizophrenia patients. Mouse dysbindin genetic defects and other mouse models of neurodevelopmental disorders share defective GABAergic neurotransmission and, in several instances, a loss of parvalbumin-positive interneuron phenotypes. This suggests that mechanisms downstream of dysbindin deficiency, such as those affecting GABA interneurons, could inform pathways contributing to or ameliorating diverse neurodevelopmental disorders...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28337033/cortical-cells-reveal-app-as-a-new-player-in-the-regulation-of-gabaergic-neurotransmission
#2
Anna Doshina, Florian Gourgue, Michiho Onizuka, Remi Opsomer, Peng Wang, Kunie Ando, Bernadette Tasiaux, Ilse Dewachter, Pascal Kienlen-Campard, Jean-Pierre Brion, Philippe Gailly, Jean-Noël Octave, Nathalie Pierrot
The amyloid precursor protein (APP) modulates synaptic activity, resulting from the fine tuning of excitatory and inhibitory neurotransmission. GABAergic inhibitory neurotransmission is affected by modifications in intracellular chloride concentrations regulated by Na(+)-K(+)-2Cl(-) cotransporter 1 (NKCC1) and neuronal K(+)-Cl(-) cotransporter 2 (KCC2), allowing entrance and efflux of chloride, respectively. Modifications in NKCC1 and KCC2 expression during maturation of cortical cells induce a shift in GABAergic signaling...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28336934/low-frequency-stimulation-of-the-primary-focus-retards-positive-transfer-of-secondary-focus
#3
Yifang Kuang, Cenglin Xu, Yinxi Zhang, Yi Wang, Xiaohua Wu, Ying Wang, Yao Liu, Kai Zhong, Hui Cheng, Yi Guo, Shuang Wang, Meiping Ding, Zhong Chen
Positive transfer of secondary focus (PTS) refers to new epileptogenesis outside the primary focus and is minimally controlled by existing treatments. Low-frequency stimulation (LFS) has benefits on the onset of epilepsy and epileptogenesis. However, it's unclear whether LFS can retard the PTS in epilepsy. Here we found that PTS at both contralateral amygdala and ipsilateral hippocampus were promoted after the primary focus was fully kindled in rat kindling model. The promotion of PTS at the mirror focus started when the primary kindling acquisition reached focal seizures...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28301408/k-cl-cotransporter-2-mediated-cl-extrusion-determines-developmental-stage-dependent-impact-of-propofol-anesthesia-on-dendritic-spines
#4
Martin Puskarjov, Hubert Fiumelli, Adrian Briner, Timea Bodogan, Kornel Demeter, Claudia-Marvine Lacoh, Martina Mavrovic, Peter Blaesse, Kai Kaila, Laszlo Vutskits
BACKGROUND: General anesthetics potentiating γ-aminobutyric acid (GABA)-mediated signaling are known to induce a persistent decrement in excitatory synapse number in the cerebral cortex when applied during early postnatal development, while an opposite action is produced at later stages. Here, the authors test the hypothesis that the effect of general anesthetics on synaptogenesis depends upon the efficacy of GABA receptor type A (GABAA)-mediated inhibition controlled by the developmental up-regulation of the potassium-chloride (K-Cl) cotransporter 2 (KCC2)...
March 16, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28279020/kcc2-downregulation-facilitates-epileptic-seizures
#5
Lulan Chen, Li Wan, Zheng Wu, Wanting Ren, Yian Huang, Binbin Qian, Yun Wang
GABAA receptor-mediated inhibition depends on the maintenance of low level intracellular [Cl(-)] concentration, which in adult depends on neuron specific K(+)-Cl(-) cotransporter-2 (KCC2). Previous studies have shown that KCC2 was downregulated in both epileptic patients and various epileptic animal models. However, the temporal relationship between KCC2 downregulation and seizure induction is unclear yet. In this study, we explored the temporal relationship and the influence of KCC2 downregulation on seizure induction...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28235805/a-kainate-receptor-subunit-promotes-the-recycling-of-the-neuron-specific-k-cl-cotransporter-kcc2-in-hippocampal-neurons
#6
Jessica C Pressey, Vivek Mahadevan, C Sahara Khademullah, Zahra Dargaei, Jonah Chevrier, Alamjeet K Chauhan, Steven J Meas, Pavel Uvarov, Matti S Airaksinen, Melanie A Woodin
Synaptic inhibition depends on a transmembrane gradient of chloride, which is set by the neuron-specific K+-Cl- cotransporter KCC2. Reduced KCC2 levels in the neuronal membrane contribute to the generation of epilepsy, neuropathic pain, and autism spectrum disorders; thus, it is important to characterize the mechanisms regulating KCC2 expression. In the present study, we determined the role of KCC2-protein interactions in regulating total and surface-membrane KCC2 expression. Using quantitative immunofluorescence in cultured mouse hippocampal neurons, we discovered that the kainate receptor subunit GluK2 and the auxiliary subunit Neto2 significantly increase the total KCC2 abundance in neurons, but that GluK2 exclusively increases the abundance of KCC2 in the surface membrane...
February 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28223240/carbachol-induced-network-oscillations-in-an-in-vitro-limbic-system-brain-slice
#7
Maxime Lévesque, Mauro Cataldi, Li-Yuan Chen, Shabnam Hamidi, Massimo Avoli
We employed simultaneous field potential recordings from CA3, subiculum and entorhinal cortex in an in vitro brain slice preparation to understand the involvement of these limbic areas in the generation of the field potential oscillations that are induced by bath application of the muscarinic receptor agonist carbachol. Regularly spaced oscillations that mainly presented at theta frequency range (5-12Hz) occurred synchronously in all three structures in the presence of carbachol. These oscillations, which disappeared when slices were perfused with pirenzepine or with glutamatergic receptor antagonists, were categorized as short (<4s) and long (>4s) with short events oscillating at higher frequencies than long events...
February 21, 2017: Neuroscience
https://www.readbyqxmd.com/read/28143398/a-noninvasive-optical-approach-for-assessing-chloride-extrusion-activity-of-the-k-cl-cotransporter-kcc2-in-neuronal-cells
#8
Anastasia Ludwig, Claudio Rivera, Pavel Uvarov
BACKGROUND: Cation-chloride cotransporters (CCCs) are indispensable for maintaining chloride homeostasis in multiple cell types, but K-Cl cotransporter KCC2 is the only CCC member with an exclusively neuronal expression in mammals. KCC2 is critical for rendering fast hyperpolarizing responses of ionotropic γ-aminobutyric acid and glycine receptors in adult neurons, for neuronal migration in the developing central nervous system, and for the formation and maintenance of small dendritic protrusions-dendritic spines...
January 31, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/28101155/the-5-ht2a-receptor-potassium-chloride-cotransporter-2-signaling-pathway-in-a-rat-incision-pain-model
#9
Rong Dong, Buwei Yu, Lijiao Chen, Weifeng Yu
Postoperative pain is a critical problem in clinical pain administration. Due to the unclear formation mechanism of postoperative pain, the treatment of postoperative pain is still in the symptomatic treatment stage and lacking satisfactory analgesic effect. Postoperative pain can be simulated by using a rat incision pain model. We observed changes in pain-related behavior of rats affected by the 5-hydroxytryptamine 2A receptor (5-HT2AR) agonist, TCB-2, and antagonist, ketanserin, through intrathecal delivery...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28074534/depolarizing-gaba-contributes-to-glutamatergic-network-rewiring-in-epilepsy
#10
Nazim Kourdougli, Christophe Pellegrino, Juho-Matti Renko, Stanislav Khirug, Geneviève Chazal, Tiina-Kaisa Kukko-Lukjanov, Sari E Lauri, Jean-Luc Gaiarsa, Liang Zhou, Angélique Peret, Eero Castrén, Raimo Kalevi Tuominen, Valérie Crépel, Claudio Rivera
OBJECTIVE: Rewiring of excitatory glutamatergic neuronal circuits is a major abnormality in epilepsy. Besides the rewiring of excitatory circuit, an abnormal depolarizing GABAergic drive has been hypothesized to participate in the epileptogenic processes. However, a remaining clinically relevant question is whether early post Status Epilepticus (SE) evoked chloride dysregulation is important for the remodeling of aberrant glutamatergic neuronal circuit. METHODS: Osmotic mini-pumps were used to infuse intracerebrally a specific inhibitor of depolarizing GABAergic transmission as well as a functionally blocking antibody towards the pan-neurotrophin receptor p75 (p75(NTR) )...
January 11, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28057537/the-chloride-co-transporters-nkcc1-and-kcc2-in-experimental-autoimmune-encephalomyelitis-eae
#11
Muhammad Saad Yousuf, Kasia Zubkow, Gustavo Tenorio, Bradley Kerr
Patients with multiple sclerosis (MS) often complain of neuropathic pain. According to the Gate Control Theory of Pain, spinal networks of GABAergic inhibitory interneurons are important in modulating nociceptive inputs from the periphery. Na+-K+-2Cl- co-transporter 1 (NKCC1) and K+-Cl- co-transporter 2 (KCC2) generally dictate the tone of GABA/glycine inhibition by regulating intracellular chloride concentrations. In this study, we investigated the role of NKCC1 and KCC2 in neuropathic pain observed in the animal model, experimental autoimmune encephalomyelitis (EAE), a commonly used model to study the pathophysiology of MS...
March 6, 2017: Neuroscience
https://www.readbyqxmd.com/read/28054918/app-modulates-kcc2-expression-and-function-in-hippocampal-gabaergic-inhibition
#12
Ming Chen, Jinzhao Wang, Jinxiang Jiang, Xingzhi Zheng, Nicholas J Justice, Kun Wang, Xiangqian Ran, Yi Li, Qingwei Huo, Jiajia Zhang, Hongmei Li, Nannan Lu, Ying Wang, Hui Zheng, Cheng Long, Li Yang
Amyloid precursor protein (APP) is enriched at the synapse, but its synaptic function is still poorly understood. We previously showed that GABAergic short-term plasticity is impaired in App knock-out (App(-/-)) animals, but the precise mechanism by which APP regulates GABAergic synaptic transmission has remained elusive. Using electrophysiological, biochemical, moleculobiological, and pharmacological analysis, here we show that APP can physically interact with KCC2, a neuron-specific K(+)-Cl(-) cotransporter that is essential for Cl(-) homeostasis and fast GABAergic inhibition...
January 5, 2017: ELife
https://www.readbyqxmd.com/read/28032116/synaptic-inhibition-in-avian-interaural-level-difference-sound-localizing-neurons
#13
Rebecca J Curry, Yong Lu
Synaptic inhibition plays a fundamental role in the neural computation of the interaural level difference (ILD), an important cue for the localization of high-frequency sound. Here, we studied the inhibitory synaptic currents in the chicken posterior portion of the dorsal nucleus of the lateral lemniscus (LLDp), the first binaural level difference encoder of the avian auditory pathway. Using whole-cell recordings in brain slices, we provide the first evidence confirming a monosynaptic inhibition driven by direct electrical and chemical stimulation of the contralateral LLDp, establishing the reciprocal inhibitory connection between the two LLDps, a long-standing assumption in the field...
November 2016: ENeuro
https://www.readbyqxmd.com/read/27998063/challenges-of-finding-novel-drugs-targeting-the-k-cl-cotransporter
#14
Eric Delpire, C David Weaver
Human disease-causing mutations and genetically modified mouse models have established the importance of KCC2 and KCC3 in nervous system physiology. These two proteins mediate the electroneutral cotransport of K(+) and Cl(-) ions across the neuronal membrane. Disruption of KCC2 function affects inhibitory synaptic transmission with consequences for epilepsy, pain perception, and potentially some neuropsychiatric disorders, whereas disruption of KCC3 affects both central and peripheral nervous systems, resulting in psychosis and peripheral neuropathy...
December 21, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27935475/thalamo-cortical-axons-regulate-the-radial-dispersion-of-neocortical-gabaergic-interneurons
#15
Sabrina Zechel, Yasushi Nakagawa, Carlos F Ibáñez
Neocortical GABAergic interneuron migration and thalamo-cortical axon (TCA) pathfinding follow similar trajectories and timing, suggesting they may be interdependent. The mechanisms that regulate the radial dispersion of neocortical interneurons are incompletely understood. Here we report that disruption of TCA innervation, or TCA-derived glutamate, affected the laminar distribution of GABAergic interneurons in mouse neocortex, resulting in abnormal accumulation in deep layers of interneurons that failed to switch from tangential to radial orientation...
December 9, 2016: ELife
https://www.readbyqxmd.com/read/27913431/pro-brain-derived-neurotrophic-factor-probdnf-mediated-p75ntr-activation-promotes-depolarizing-actions-of-gaba-and-increases-susceptibility-to-epileptic-seizures
#16
Baptiste Riffault, Nazim Kourdougli, Camille Dumon, Nadine Ferrand, Emmanuelle Buhler, Fabienne Schaller, Caroline Chambon, Claudio Rivera, Jean-Luc Gaiarsa, Christophe Porcher
The brain-derived neurotrophic factor (BDNF) is synthesized as a precursor, namely proBDNF, which can be processed into mature BDNF (mBDNF). Evidences suggest that proBDNF signaling through p75(NTR) may account for the emergence of neurological disorders. These findings support the view that the relative availability of mBDNF and proBDNF forms is an important mechanism underlying brain circuit formation and cognitive functions. Here we describe novel insights into the proBDNF/p75(NTR) mechanisms and function in vivo in modulating neuronal circuit and synaptic plasticity during the first postnatal weeks in rats...
December 1, 2016: Cerebral Cortex
https://www.readbyqxmd.com/read/27881775/a-biophysical-model-for-cytotoxic-cell-swelling
#17
Koen Dijkstra, Jeannette Hofmeijer, Stephan A van Gils, Michel J A M van Putten
We present a dynamic biophysical model to explain neuronal swelling underlying cytotoxic edema in conditions of low energy supply, as observed in cerebral ischemia. Our model contains Hodgkin-Huxley-type ion currents, a recently discovered voltage-gated chloride flux through the ion exchanger SLC26A11, active KCC2-mediated chloride extrusion, and ATP-dependent pumps. The model predicts changes in ion gradients and cell swelling during ischemia of various severity or channel blockage with realistic timescales...
November 23, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27871891/long-term-alcohol-exposure-elicits-hippocampal-nonsynaptic-epileptiform-activity-changes-associated-with-expression-and-functional-changes-in-nkcc1-kcc2-co-transporters-and-na-k-atpase
#18
Luiz E C Santos, Antônio M Rodrigues, Mariana R Lopes, Victor D C Costa, Carla A Scorza, Fulvio A Scorza, Esper A Cavalheiro, Antônio-Carlos G Almeida
Nonsynaptic mechanism changes, particularly the enhancement of NKCC1 expression in the dentate gyrus (DG) after 4weeks of ethanol consumption, motivate the present work, in which rats were submitted to a period of chronic consumption (12weeks). Four groups of six animals (6-week-old male Wistar rats) were formed, including the control (C), ethanol 1 (E1), ethanol 2 (E2) and ethanol 3 (E3) groups. The rats in the E1, E2 and E3 groups were treated daily with a 30% v/v solution of ethanol, administered via oral gavage (1...
January 6, 2017: Neuroscience
https://www.readbyqxmd.com/read/27861901/chloride-co-transporters-as-possible-therapeutic-targets-for-stroke
#19
REVIEW
Miguel A S Martín-Aragón Baudel, Amy V Poole, Mark G Darlison
Stroke is one of the major causes of death and disability worldwide. The major type of stroke is an ischaemic one, which is caused by a blockage that interrupts blood flow to the brain. There are currently very few pharmacological strategies to reduce the damage and social burden triggered by this pathology. The harm caused by the interruption of blood flow to the brain unfolds in the subsequent hours and days, so it is critical to identify new therapeutic targets that could reduce neuronal death associated with the spread of the damage...
November 15, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27852771/reduced-efficacy-of-the-kcc2-cotransporter-promotes-epileptic-oscillations-in-a-subiculum-network-model
#20
Anatoly Buchin, Anton Chizhov, Gilles Huberfeld, Richard Miles, Boris S Gutkin
Pharmacoresistant epilepsy is a chronic neurological condition in which a basal brain hyperexcitability results in paroxysmal hypersynchronous neuronal discharges. Human temporal lobe epilepsy has been associated with dysfunction or loss of the potassium-chloride cotransporter KCC2 in a subset of pyramidal cells in the subiculum, a key structure generating epileptic activities. KCC2 regulates intraneuronal chloride and extracellular potassium levels by extruding both ions. Absence of effective KCC2 may alter the dynamics of chloride and potassium levels during repeated activation of GABAergic synapses due to interneuron activity...
November 16, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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