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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
#1
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
#2
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
#3
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...
November 18, 2016: Neuroscience
https://www.readbyqxmd.com/read/27861901/chloride-co-transporters-as-possible-therapeutic-targets-for-stroke
#4
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
#5
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
https://www.readbyqxmd.com/read/27818188/complete-spinal-cord-injury-sci-transforms-how-brain-derived-neurotrophic-factor-bdnf-affects-nociceptive-sensitization
#6
Yung-Jen Huang, Kuan H Lee, James W Grau
Noxious stimulation can induce a lasting increase in neural excitability within the spinal cord (central sensitization) that can promote pain and disrupt adaptive function (maladaptive plasticity). Brain-derived neurotrophic factor (BDNF) is known to regulate the development of plasticity and has been shown to impact the development of spinally-mediated central sensitization. The latter effect has been linked to an alteration in GABA-dependent inhibition. Prior studies have shown that, in spinally transected rats, exposure to regular (fixed spaced) stimulation can counter the development of maladaptive plasticity and have linked this effect to an up-regulation of BDNF...
November 3, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27818163/down-regulation-of-zinc-transporter-1-in-astrocytes-induces-neuropathic-pain-via-the-brain-derived-neurotrophic-factor-k-cl-co-transporter-2-signaling-pathway-in-the-mouse-spinal-cord
#7
Tomoya Kitayama, Katsuya Morita, Naoyo Motoyama, Toshihiro Dohi
We previously demonstrated, using a DNA microarray analysis, the down-regulated expression of the slc30a1 gene (zinc transporter 1, ZnT1) in a neuropathic pain model induced by partial sciatic nerve ligation (PSNL). Zinc is an essential trace mineral that plays important roles in physiological functions, and ZnT1 modulates intracellular zinc levels. In the present study, we examined the effects of the down-regulation of the ZnT1 gene in the spinal cord on tactile allodynia. The knockdown (KD) of ZnT1 by the intrathecal administration of siRNA against ZnT1 to mice induced allodynia, a characteristic syndrome of neuropathic pain, which persisted for at least one month...
December 2016: Neurochemistry International
https://www.readbyqxmd.com/read/27803317/jointly-reduced-inhibition-and-excitation-underlies-circuit-wide-changes-in-cortical-processing-in-rett-syndrome
#8
Abhishek Banerjee, Rajeev V Rikhye, Vincent Breton-Provencher, Xin Tang, Chenchen Li, Keji Li, Caroline A Runyan, Zhanyan Fu, Rudolf Jaenisch, Mriganka Sur
Rett syndrome (RTT) arises from loss-of-function mutations in methyl-CpG binding protein 2 gene (Mecp2), but fundamental aspects of its physiological mechanisms are unresolved. Here, by whole-cell recording of synaptic responses in MeCP2 mutant mice in vivo, we show that visually driven excitatory and inhibitory conductances are both reduced in cortical pyramidal neurons. The excitation-to-inhibition (E/I) ratio is increased in amplitude and prolonged in time course. These changes predict circuit-wide reductions in response reliability and selectivity of pyramidal neurons to visual stimuli, as confirmed by two-photon imaging...
November 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27793697/development-and-experience-dependent-plasticity-in-the-dorsomedial-habenula
#9
Peter Koppensteiner, Christopher Galvin, Ipe Ninan
Of the two major subdivisions of the habenula, the medial and lateral nuclei, the medial habenula is the least understood in terms of synaptic transmission, intrinsic properties and plasticity. The medial habenula (MHb) is composed of glutamatergic neurons which receive the majority of their inputs from the septal region and project predominantly to the interpeduncular nucleus (IPN). To understand the synaptic transmission, we studied both glutamatergic and GABAergic synaptic transmission in the dorsal region of the medial habenula (dMHb)...
December 2016: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/27788626/when-pain-hurts-nociceptive-stimulation-induces-a-state-of-maladaptive-plasticity-and-impairs-recovery-after-spinal-cord-injury
#10
James W Grau, Yung-Jen Huang, Joel D Turtle, Misty M Strain, Rajesh C Miranda, Sandra M Garraway, Michelle Hook
Spinal cord injury (SCI) is often accompanied by other tissue damage (polytrauma) that provides a source of pain (nociceptive) input. Recent findings are reviewed that show SCI places the caudal tissue in a vulnerable state that exaggerates the effects nociceptive stimuli and promotes the development of nociceptive sensitization. Stimulation that is both unpredictable and uncontrollable induces a form of maladaptive plasticity that enhances nociceptive sensitization and impairs spinally-mediated learning. In contrast, relational learning induces a form of adaptive plasticity that counters these adverse effects...
October 27, 2016: Journal of Neurotrauma
https://www.readbyqxmd.com/read/27780732/altered-postnatal-maturation-of-striatal-gabaergic-interneurons-in-a-phenotypic-animal-model-of-dystonia
#11
Christoph Bode, Franziska Richter, Christine Spröte, Tanja Brigadski, Anne Bauer, Simone Fietz, Jean-Marc Fritschy, Angelika Richter
GABAergic disinhibition has been suggested to play a critical role in the pathophysiology of several basal ganglia disorders, including dystonia, a common movement disorder. Previous studies have shown a deficit of striatal GABAergic interneurons (IN) in the dt(sz) mutant hamster, one of the few phenotypic animal models of dystonia. However, mechanisms underlying this deficit are largely unknown. In the present study, we investigated the migration and maturation of striatal IN during postnatal development (18days of age) and at age of highest severity of dystonia (33days of age) in this hamster model...
January 2017: Experimental Neurology
https://www.readbyqxmd.com/read/27778437/increase-of-kcc2-in-hippocampal-synaptic-plasticity-disturbances-after-perinatal-ethanol-exposure
#12
Benoît Silvestre de Ferron, Catherine Vilpoux, Myriam Kervern, Alexandre Robert, Johan Antol, Mickael Naassila, Olivier Pierrefiche
Low to moderate perinatal ethanol exposure (PEE) may have disastrous consequences for the central nervous system resulting notably in permanent cognitive deficits. Learning and memory are mediated in the hippocampus by long-term potentiation (LTP) and long term depression (LTD), two forms of synaptic plasticity. PEE decreases LTP but also abnormally facilitates LTD (Kervern et al. ) through a presently unknown mechanism. We studied in rat hippocampus slice, the involvement of the chloride co-transporters NKCC1 and KCC2, in the role of GABAA inhibitions in facilitated LTD after moderate PEE...
October 25, 2016: Addiction Biology
https://www.readbyqxmd.com/read/27720487/stress-increases-ethanol-self-administration-via-a-shift-toward-excitatory-gaba-signaling-in-the-ventral-tegmental-area
#13
Alexey Ostroumov, Alyse M Thomas, Blake A Kimmey, Jordan S Karsch, William M Doyon, John A Dani
Stress is a well-known risk factor for subsequent alcohol abuse, but the neural mechanisms underlying interactions between stress and alcohol remain largely unknown. Addictive drug reinforcement and stress signaling involve common neural circuitry, including the mesolimbic dopamine system. We demonstrate in rodents that pre-exposure to stress attenuates alcohol-induced dopamine responses and increases alcohol self-administration. The blunted dopamine signaling resulted from ethanol-induced excitation of GABA neurons in the ventral tegmental area...
October 19, 2016: Neuron
https://www.readbyqxmd.com/read/27688312/pulsed-radiofrequency-attenuates-complete-freund-s-adjuvant-induced-epigenetic-suppression-of-potassium-chloride-cotransporter-2-expression
#14
Chia-Kai Liu, Wen-Tzu Liao, Yu-Chi Chu, Chien-Hui Yang, Kuan-Hung Chen, Chih-Hsien Wu, Chung-Ren Lin
BACKGROUND:  Pulsed radiofrequency (PRF) treatment offers pain relief for patients suffering from chronic pain who do not respond well to conventional treatments. We tested whether PRF treatment attenuated complete Freund's adjuvant (CFA)-induced inflammatory pain. Epigenetic modification of potassium-chloride cotransporter 2 (KCC2) gene expression was examined to elucidate the potential contributing mechanism. METHODS:  Male Sprague-Dawley rats were injected with CFA into the plantar surface of the left hind paw to induce inflammation...
September 28, 2016: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/27639636/acute-spinal-cord-injury-sci-transforms-how-gaba-affects-nociceptive-sensitization
#15
Yung-Jen Huang, Kuan H Lee, Lauren Murphy, Sandra M Garraway, James W Grau
Noxious input can sensitize pain (nociceptive) circuits within the spinal cord, inducing a lasting increase in spinal cord neural excitability (central sensitization) that is thought to contribute to chronic pain. The development of spinally-mediated central sensitization is regulated by descending fibers and GABAergic interneurons. The current study provides evidence that spinal cord injury (SCI) transforms how GABA affects nociceptive transmission within the spinal cord, recapitulating an earlier developmental state wherein GABA has an excitatory effect...
November 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27630564/reactive-neurogenesis-and-down-regulation-of-the-potassium-chloride-cotransporter-kcc2-in-the-cochlear-nuclei-after-cochlear-deafferentation
#16
Brahim Tighilet, Sophie Dutheil, Marina I Siponen, Arnaud J Noreña
While many studies have been devoted to investigating the homeostatic plasticity triggered by cochlear hearing loss, the cellular and molecular mechanisms involved in these central changes remain elusive. In the present study, we investigated the possibility of reactive neurogenesis after unilateral cochlear nerve section in the cochlear nucleus (CN) of cats. We found a strong cell proliferation in all the CN sub-divisions ipsilateral to the lesion. Most of the newly generated cells survive up to 1 month after cochlear deafferentation in all cochlear nuclei (except the dorsal CN) and give rise to a variety of cell types, i...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27590453/expressions-of-ion-co-transporter-genes-in-salicylate-induced-tinnitus-and-treatment-effects-of-spirulina
#17
Juen-Haur Hwang, Yin-Ching Chan
BACKGROUND: Although the activity of tinnitus-related ion co-transporter are known, their mRNA expressions has seldom been reported. We aimed to investigate the mRNA expressions of tinnitus-related ion co-transporter genes, and treatment effects of Spirulina. METHODS: The mRNA expressions of K(+)-Cl(-) co-transporter (KCC2) and Na-K-2Cl co-transporter 1 (NKCC1) genes in the cochlea and brain of mice were evaluated after tinnitus was induced by intraperitoneal injection of salicylate...
September 2, 2016: BMC Neurology
https://www.readbyqxmd.com/read/27586142/nkcc1-up-regulation-contributes-to-early-post-traumatic-seizures-and-increased-post-traumatic-seizure-susceptibility
#18
Fushun Wang, Xiaowei Wang, Lee A Shapiro, Maria L Cotrina, Weimin Liu, Ernest W Wang, Simeng Gu, Wei Wang, Xiaosheng He, Maiken Nedergaard, Jason H Huang
Traumatic brain injury (TBI) is not only a leading cause for morbidity and mortality in young adults (Bruns and Hauser, Epilepsia 44(Suppl 10):210, 2003), but also a leading cause of seizures. Understanding the seizure-inducing mechanisms of TBI is of the utmost importance, because these seizures are often resistant to traditional first- and second-line anti-seizure treatments. The early post-traumatic seizures, in turn, are a contributing factor to ongoing neuropathology, and it is critically important to control these seizures...
September 1, 2016: Brain Structure & Function
https://www.readbyqxmd.com/read/27576299/a-novel-p2x4-receptor-selective-antagonist-produces-anti-allodynic-effect-in-a-mouse-model-of-herpetic-pain
#19
Yuta Matsumura, Tomohiro Yamashita, Atsushi Sasaki, Eriko Nakata, Keita Kohno, Takahiro Masuda, Hidetoshi Tozaki-Saitoh, Toshiyasu Imai, Yasushi Kuraishi, Makoto Tsuda, Kazuhide Inoue
Accumulating evidence indicates that purinergic P2X4 receptors (P2X4R: cation channels activated by extracellular ATP) expressed in spinal microglia are crucial for pathological chronic pain caused by nerve damage, suggesting a potential target for drug discovery. We identified NP-1815-PX (5-[3-(5-thioxo-4H-[1,2,4]oxadiazol-3-yl)phenyl]-1H-naphtho[1, 2-b][1,4]diazepine-2,4(3H,5H)-dione) as a novel antagonist selective for P2X4R with high potency and selectivity compared with other P2XR subtypes. In in vivo assay for acute and chronic pain, intrathecal administration of NP-1815-PX produced an anti-allodynic effect in mice with traumatic nerve damage without affecting acute nociceptive pain and motor function (although its oral administration did not produce the effect)...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27545000/plantar-injection-of-formalin-in-rats-reduces-the-expression-of-a-potassium-chroride-cotransporter-kcc2-in-the-spinal-cord-and-a-kinase-inhibitor-suppresses-this-reduction
#20
Kenkichi Tsuruga, Toshikazu Hashimoto, Ryoko Kato, Rui Kato, Yousuke Uchida, Tetsutaro Hase, Yuji Morimoto
Brain-derived neurotrophic factor (BDNF) is released from activated microglia during neuropathic pain and is hypothesized to downregulate the expression of the potassium chloride cotransporter 2 (KCC2) via the TrkB receptor. Previous studies reported that KCC2 is downregulated 5 min after the plantar injection of formalin in rats; however, the mechanism behind this decrease in KCC2 expression during acute inflammatory pain remains unknown. In this study, we determined whether the TrkB receptor contributes to the expression of KCC2 during the acute pain...
2016: Biomedical Research
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