Dysregulation of GABAergic Signaling in Neurodevelomental Disorders: Targeting Cation-Chloride Co-transporters to Re-establish a Proper E/I Balance

The Multifaceted Roles of KCC2 in Cortical Development

(2021) Mari A. Virtanen et al.   TRENDS IN NEUROSCIENCES

Reply to the commentary by Ben‐Ari and Delpire: Bumetanide and neonatal seizures: Fiction versus reality

(2021) Wolfgang Löscher et al.   EPILEPSIA

A limited role of NKCC1 in telencephalic glutamatergic neurons for developing hippocampal network dynamics and behavior

(2021) Jürgen Graf et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Depolarizing GABAA current in the prefrontal cortex is linked with cognitive impairment in a mouse model relevant for schizophrenia

(2021) Haram R. Kim et al.   Science Advances

Pharmacological tools to target NKCC1 in brain disorders

(2021) Annalisa Savardi et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Symptom improvement in children with autism spectrum disorder following bumetanide administration is associated with decreased GABA/glutamate ratios

(2020) Lingli Zhang et al.   Translational Psychiatry

Oxidative Stress and Immune System Dysfunction in Autism Spectrum Disorders

(2020) Luca Pangrazzi et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Whole-Neuron Synaptic Mapping Reveals Spatially Precise Excitatory/Inhibitory Balance Limiting Dendritic and Somatic Spiking

(2020) Daniel Maxim Iascone et al.   NEURON

Neurobiological Mechanisms of Autism Spectrum Disorder and Epilepsy, Insights from Animal Models

(2020) Teresa Sierra-Arregui et al.   NEUROSCIENCE

Effects of bumetanide on neurodevelopmental impairments in patients with tuberous sclerosis complex: an open-label pilot study

(2020) Dorinde M. van Andel et al.   Molecular Autism

Bumetanide for Core Symptoms of Autism Spectrum Disorder (BAMBI): A Single Center, Double-Blinded, Participant-Randomized, Placebo-Controlled, Phase Two, Superiority Trial

(2020) Jan J. Sprengers et al.   JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY

GABAergic interneurons excite neonatal hippocampus in vivo

(2020) Yasunobu Murata et al.   Science Advances

Immature Dentate Granule Cells Require Ntrk2/Trkb for the Formation of Functional Hippocampal Circuitry

(2020) Sylvia Badurek et al.   iScience

Novel Therapeutic Approach for Excitatory/Inhibitory Imbalance in Neurodevelopmental and Neurodegenerative Diseases

(2020) Swagata Ghatak et al.   Annual Review of Pharmacology and Toxicology

LTP Induction Boosts Glutamate Spillover by Driving Withdrawal of Perisynaptic Astroglia

(2020) Christian Henneberger et al.   NEURON

Bumetanide for autism: Open‐label trial in six children

(2020) Elisabeth Fernell et al.   ACTA PAEDIATRICA

A Pilot Randomized, Controlled, Double‐Blind Trial of Bumetanide to Treat Neonatal Seizures

(2020) Janet S. Soul et al.   ANNALS OF NEUROLOGY

NKCC1, an Elusive Molecular Target in Brain Development: Making Sense of the Existing Data

(2020) Mari A. Virtanen et al.   Cells

Expression of GSK3β, PICK1, NEFL, C4, NKCC1 and Synaptophysin in peripheral blood mononuclear cells of the first-episode schizophrenia patients

(2020) Tingting zhang et al.   Asian Journal of Psychiatry

KCC2 chloride transport contributes to the termination of ictal epileptiform activity

(2020) Volodymyr I. Dzhala et al.   eNeuro

KCC2-Mediated Cl− Extrusion Modulates Spontaneous Hippocampal Network Events in Perinatal Rats and Mice

(2019) Inkeri Spoljaric et al.   Cell Reports

Excitation-inhibition balance as a framework for investigating mechanisms in neuropsychiatric disorders

(2019) Vikaas S. Sohal et al.   MOLECULAR PSYCHIATRY

Differential transcriptional profiles identify microglial- and macrophage-specific gene markers expressed during virus-induced neuroinflammation

(2019) Ana Beatriz DePaula-Silva et al.   Journal of Neuroinflammation

KCC2 ANTAGONISM INCREASES NEURONAL NETWORK EXCITABILITY BUT DISRUPTS ICTOGENESIS IN VITRO

(2019) Li-Yuan Chen et al.   JOURNAL OF NEUROPHYSIOLOGY

Pharmacological enhancement of KCC2 gene expression exerts therapeutic effects on human Rett syndrome neurons and Mecp2 mutant mice

(2019) Xin Tang et al.   Science Translational Medicine

Delayed maturation of GABAergic signaling in the Scn1a and Scn1b mouse models of Dravet Syndrome

(2019) Yukun Yuan et al.   Scientific Reports

Identification of KCC2 Mutations in Human Epilepsy Suggests Strategies for Therapeutic Transporter Modulation

(2019) Phan Q. Duy et al.   Frontiers in Cellular Neuroscience

Maternal Immune Activation Delays Excitatory-to-Inhibitory Gamma-Aminobutyric Acid Switch in Offspring

(2018) Irene Corradini et al.   BIOLOGICAL PSYCHIATRY

Development of inhibitory synaptic inputs on layer 2/3 pyramidal neurons in the rat medial prefrontal cortex

(2018) Mari A. Virtanen et al.   Brain Structure & Function

Brief activation of GABAergic interneurons initiates the transition to ictal events through post-inhibitory rebound excitation

(2018) Michael Chang et al.   NEUROBIOLOGY OF DISEASE

Alterations in cortical interneurons and cognitive function in schizophrenia

(2018) Samuel J. Dienel et al.   NEUROBIOLOGY OF DISEASE

Chloride transporters and GABA polarity in developmental, neurological and psychiatric conditions

(2018) Joran T. Schulte et al.   NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS

KCC2, epileptiform synchronization, and epileptic disorders

(2018) Graziella Di Cristo et al.   PROGRESS IN NEUROBIOLOGY

Bumetanide for autism: more eye contact, less amygdala activation

(2018) Nouchine Hadjikhani et al.   Scientific Reports

KCC2 Regulates Dendritic Spine Formation in a Brain-Region Specific and BDNF Dependent Manner

(2018) Patricia Nora Awad et al.   CEREBRAL CORTEX

Potentiating KCC2 activity is sufficient to limit the onset and severity of seizures

(2018) Yvonne E. Moore et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

The GABA Developmental Shift Is Abolished by Maternal Immune Activation Already at Birth

(2018) Amandine Fernandez et al.   CEREBRAL CORTEX

Interneurons and principal cell firing in human limbic areas at focal seizure onset

(2018) Shennan A. Weiss et al.   NEUROBIOLOGY OF DISEASE

Neurobiological bases of autism-epilepsy comorbidity: a focus on excitation/inhibition imbalance

(2017) Yuri Bozzi et al.   EUROPEAN JOURNAL OF NEUROSCIENCE

Interneuronal Network Activity at the Onset of Seizure-Like Events in Entorhinal Cortex Slices

(2017) Laura Librizzi et al.   JOURNAL OF NEUROSCIENCE

Dynamic, Cell-Type-Specific Roles for GABAergic Interneurons in a Mouse Model of Optogenetically Inducible Seizures

(2017) Sattar Khoshkhoo et al.   NEURON

Early IGF-1 primes visual cortex maturation and accelerates developmental switch between NKCC1 and KCC2 chloride transporters in enriched animals

(2017) Laura Baroncelli et al.   NEUROPHARMACOLOGY

Multiple blood-brain barrier transport mechanisms limit bumetanide accumulation, and therapeutic potential, in the mammalian brain

(2017) Kerstin Römermann et al.   NEUROPHARMACOLOGY

Simultaneous two-photon imaging of intracellular chloride concentration and pH in mouse pyramidal neurons in vivo

(2017) Sebastian Sulis Sato et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

NKCC1 Chloride Importer Antagonists Attenuate Many Neurological and Psychiatric Disorders

(2017) Yehezkel Ben-Ari   TRENDS IN NEUROSCIENCES

Early Correlated Network Activity in the Hippocampus: Its Putative Role in Shaping Neuronal Circuits

(2017) Marilena Griguoli et al.   Frontiers in Cellular Neuroscience

Periadolescent Maturation of GABAergic Hyperpolarization at the Axon Initial Segment

(2017) Gina Rinetti-Vargas et al.   Cell Reports

Effects of bumetanide on neurobehavioral function in children and adolescents with autism spectrum disorders

(2017) E Lemonnier et al.   Translational Psychiatry

Dysbindin Deficiency Modifies the Expression of GABA Neuron and Ion Permeation Transcripts in the Developing Hippocampus

(2017) Jennifer Larimore et al.   Frontiers in Genetics

The neuronal K+Cl− co-transporter 2 (Slc12a5) modulates insulin secretion

(2017) Shams Kursan et al.   Scientific Reports

Activation of specific neuronal networks leads to different seizure onset types

(2016) Zahra Shiri et al.   ANNALS OF NEUROLOGY

Specific imbalance of excitatory/inhibitory signaling establishes seizure onset pattern in temporal lobe epilepsy

(2016) Massimo Avoli et al.   JOURNAL OF NEUROPHYSIOLOGY

An Optogenetic Approach for Investigation of Excitatory and Inhibitory Network GABA Actions in Mice Expressing Channelrhodopsin-2 in GABAergic Neurons

(2016) Guzel Valeeva et al.   JOURNAL OF NEUROSCIENCE

Gain-of-function missense variant in SLC12A2, encoding the bumetanide-sensitive NKCC1 cotransporter, identified in human schizophrenia

(2016) Nancy D. Merner et al.   JOURNAL OF PSYCHIATRIC RESEARCH

Compromising KCC2 transporter activity enhances the development of continuous seizure activity

(2016) Matthew R. Kelley et al.   NEUROPHARMACOLOGY

De novo synaptogenesis induced by GABA in the developing mouse cortex

(2016) Won Chan Oh et al.   SCIENCE

The Timing of the Excitatory-to-Inhibitory GABA Switch Is Regulated by the Oxytocin Receptor via KCC2

(2016) Marianna Leonzino et al.   Cell Reports

Interneuron activity leads to initiation of low-voltage fast-onset seizures

(2015) Zahra Shiri et al.   ANNALS OF NEUROLOGY

Antioxidants and NOS inhibitors selectively targets manganese-induced cell volume via Na–K–Cl cotransporter-1 in astrocytes

(2015) Khalid A Alahmari et al.   BRAIN RESEARCH

Developmental Expression Patterns of KCC2 and Functionally Associated Molecules in the Human Brain

(2015) Goran Sedmak et al.   CEREBRAL CORTEX

A Pilot Study on the Combination of Applied Behavior Analysis and Bumetanide Treatment for Children with Autism

(2015) Lin Du et al.   JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY

Selective activation of parvalbumin- or somatostatin-expressing interneurons triggers epileptic seizurelike activity in mouse medial entorhinal cortex

(2015) Latefa Yekhlef et al.   JOURNAL OF NEUROPHYSIOLOGY

Selective Inhibition of KCC2 Leads to Hyperexcitability and Epileptiform Discharges in Hippocampal Slices and In Vivo

(2015) S. Sivakumaran et al.   JOURNAL OF NEUROSCIENCE

Evaluating historical candidate genes for schizophrenia

(2015) M S Farrell et al.   MOLECULAR PSYCHIATRY

KCC2 function modulates in vitro ictogenesis

(2015) Shabnam Hamidi et al.   NEUROBIOLOGY OF DISEASE

Carbonic anhydrase inhibition by acetazolamide reduces in vitro epileptiform synchronization

(2015) Shabnam Hamidi et al.   NEUROPHARMACOLOGY

BDNF is required for seizure-induced but not developmental up-regulation of KCC2 in the neonatal hippocampus

(2015) Martin Puskarjov et al.   NEUROPHARMACOLOGY

Paradoxical Benzodiazepine Response: A Rationale for Bumetanide in Neurodevelopmental Disorders?

(2015) H. Bruining et al.   PEDIATRICS

KCC2 activity is critical in limiting the onset and severity of status epilepticus

(2015) Liliya Silayeva et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Hippocampus and epilepsy: Findings from human tissues

(2015) G. Huberfeld et al.   REVUE NEUROLOGIQUE

GABA depolarizes immature neurons and inhibits network activity in the neonatal neocortex in vivo

(2015) Knut Kirmse et al.   Nature Communications

Decreased Chloride Channel Expression in the Dorsolateral Prefrontal Cortex in Schizophrenia

(2015) Courtney R. Sullivan et al.   PLoS One

Basic Mechanisms of Epileptogenesis in Pediatric Cortical Dysplasia

(2014) Sara Abdijadid et al.   CNS Neuroscience & Therapeutics

Genetically encoded impairment of neuronal KCC2 cotransporter function in human idiopathic generalized epilepsy

(2014) K. T. Kahle et al.   EMBO REPORTS

A variant of KCC2 from patients with febrile seizures impairs neuronal Cl- extrusion and dendritic spine formation

(2014) M. Puskarjov et al.   EMBO REPORTS

Pharmacotherapeutic targeting of cation-chloride cotransporters in neonatal seizures

(2014) Martin Puskarjov et al.   EPILEPSIA

Characteristics of the Cation Cotransporter NKCC1 in Human Brain: Alternate Transcripts, Expression in Development, and Potential Relationships to Brain Function and Schizophrenia

(2014) Y. Morita et al.   JOURNAL OF NEUROSCIENCE

Biological insights from 108 schizophrenia-associated genetic loci

(2014)   NATURE

Cation-chloride cotransporters in neuronal development, plasticity and disease

(2014) Kai Kaila et al.   NATURE REVIEWS NEUROSCIENCE

Oxytocin-Mediated GABA Inhibition During Delivery Attenuates Autism Pathogenesis in Rodent Offspring

(2014) R. Tyzio et al.   SCIENCE

Fast-spiking, parvalbumin+ GABAergic interneurons: From cellular design to microcircuit function

(2014) H. Hu et al.   SCIENCE

GABAergic Signaling as Therapeutic Target for Autism Spectrum Disorders

(2014) Giada Cellot et al.   Frontiers in Pediatrics

Intracranial electroencephalographic seizure-onset patterns: effect of underlying pathology

(2013) Piero Perucca et al.   BRAIN

Chloride extrusion enhancers as novel therapeutics for neurological diseases

(2013) Martin Gagnon et al.   NATURE MEDICINE

Modulation of neuronal activity by phosphorylation of the K–Cl cotransporter KCC2

(2013) Kristopher T. Kahle et al.   TRENDS IN NEUROSCIENCES

An unexpected role of neuroligin-2 in regulating KCC2 and GABA functional switch

(2013) Chicheng Sun et al.   Molecular Brain

Schizophrenia Is a Cognitive Illness

(2013) René S. Kahn et al.   JAMA Psychiatry

Evidence for Shared Susceptibility to Epilepsy and Psychosis: A Population-Based Family Study

(2012) Mary C. Clarke et al.   BIOLOGICAL PSYCHIATRY

Interplay between DISC1 and GABA Signaling Regulates Neurogenesis in Mice and Risk for Schizophrenia

(2012) Ju Young Kim et al.   CELL

An Ion Transport-Independent Role for the Cation-Chloride Cotransporter KCC2 in Dendritic Spinogenesis In Vivo

(2012) H. Fiumelli et al.   CEREBRAL CORTEX

Two Seizure-Onset Types Reveal Specific Patterns of High-Frequency Oscillations in a Model of Temporal Lobe Epilepsy

(2012) M. Levesque et al.   JOURNAL OF NEUROSCIENCE

The GABA Excitatory/Inhibitory Shift in Brain Maturation and Neurological Disorders

(2012) Yehezkel Ben-Ari et al.   NEUROSCIENTIST

Activation of 5-HT2A receptors upregulates the function of the neuronal K-Cl cotransporter KCC2

(2012) R. Bos et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

A randomised controlled trial of bumetanide in the treatment of autism in children

(2012) E Lemonnier et al.   Translational Psychiatry

Expression of GABA Signaling Molecules KCC2, NKCC1, and GAD1 in Cortical Development and Schizophrenia

(2011) T. M. Hyde et al.   JOURNAL OF NEUROSCIENCE

Early Growth Response 4 Mediates BDNF Induction of Potassium Chloride Cotransporter 2 Transcription

(2011) A. Ludwig et al.   JOURNAL OF NEUROSCIENCE

Neocortical excitation/inhibition balance in information processing and social dysfunction

(2011) Ofer Yizhar et al.   NATURE

Alterations in the expression of neuronal chloride transporters may contribute to schizophrenia

(2011) Hans O. Kalkman   PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY

GABAergic synchronization in the limbic system and its role in the generation of epileptiform activity

(2011) Massimo Avoli et al.   PROGRESS IN NEUROBIOLOGY

Alterations of GABAergic Signaling in Autism Spectrum Disorders

(2011) Rocco Pizzarelli et al.   NEURAL PLASTICITY

Neurturin Evokes MAPK-Dependent Upregulation of Egr4 and KCC2 in Developing Neurons

(2011) Anastasia Ludwig et al.   NEURAL PLASTICITY

The diuretic bumetanide decreases autistic behaviour in five infants treated during 3 months with no side effects

(2010) Eric Lemonnier et al.   ACTA PAEDIATRICA

Altered Expression of Regulators of the Cortical Chloride Transporters NKCC1 and KCC2 in Schizophrenia

(2010) Dominique Arion et al.   ARCHIVES OF GENERAL PSYCHIATRY

Independent Epileptiform Discharge Patterns in the Olfactory and Limbic Areas of the In Vitro Isolated Guinea Pig Brain During 4-Aminopyridine Treatment

(2010) Giovanni Carriero et al.   JOURNAL OF NEUROPHYSIOLOGY

A Single Seizure Episode Leads to Rapid Functional Activation of KCC2 in the Neonatal Rat Hippocampus

(2010) S. Khirug et al.   JOURNAL OF NEUROSCIENCE

The K+-Cl−cotransporter KCC2 promotes GABAergic excitation in the mature rat hippocampus

(2010) Tero Viitanen et al.   JOURNAL OF PHYSIOLOGY-LONDON

Abnormal neural oscillations and synchrony in schizophrenia

(2010) Peter J. Uhlhaas et al.   NATURE REVIEWS NEUROSCIENCE

Gamma Oscillatory Power is Impaired During Cognitive Control Independent of Medication Status in First-Episode Schizophrenia

(2010) Michael J Minzenberg et al.   NEUROPSYCHOPHARMACOLOGY

Chloride regulation in the pain pathway

(2009) Theodore J. Price et al.   BRAIN RESEARCH REVIEWS

Sites of Regulated Phosphorylation that Control K-Cl Cotransporter Activity

(2009) Jesse Rinehart et al.   CELL

At Immature Mossy-Fiber-CA3 Synapses, Correlated Presynaptic and Postsynaptic Activity Persistently Enhances GABA Release and Network Excitability via BDNF and cAMP-Dependent PKA

(2009) S. Sivakumaran et al.   JOURNAL OF NEUROSCIENCE

Parvalbumin neurons and gamma rhythms enhance cortical circuit performance

(2009) Vikaas S. Sohal et al.   NATURE

Driving fast-spiking cells induces gamma rhythm and controls sensory responses

(2009) Jessica A. Cardin et al.   NATURE

KCC2 Expression Promotes the Termination of Cortical Interneuron Migration in a Voltage-Sensitive Calcium-Dependent Manner

(2009) Dante Bortone et al.   NEURON

Cation-Chloride Cotransporters and Neuronal Function

(2009) Peter Blaesse et al.   NEURON

GABAergic Hub Neurons Orchestrate Synchrony in Developing Hippocampal Networks

(2009) P. Bonifazi et al.   SCIENCE

Identifying Cognitive Mechanisms Targeted for Treatment Development in Schizophrenia: An Overview of the First Meeting of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia Initiative

(2008) Cameron S. Carter et al.   BIOLOGICAL PSYCHIATRY

Coincident pre- and postsynaptic activity downregulates NKCC1 to hyperpolarize EClduring development

(2008) Trevor Balena et al.   EUROPEAN JOURNAL OF NEUROSCIENCE

GABAergic Depolarization of the Axon Initial Segment in Cortical Principal Neurons Is Caused by the Na-K-2Cl Cotransporter NKCC1

(2008) S. Khirug et al.   JOURNAL OF NEUROSCIENCE

Low expression of Kv7/M channels facilitates intrinsic and network bursting in the developing rat hippocampus

(2008) Victoria F. Safiulina et al.   JOURNAL OF PHYSIOLOGY-LONDON

A Genome-Wide Association Study of Schizophrenia Using Brain Activation as a Quantitative Phenotype

(2008) Steven G. Potkin et al.   SCHIZOPHRENIA BULLETIN

GABA Neurons and the Mechanisms of Network Oscillations: Implications for Understanding Cortical Dysfunction in Schizophrenia

(2008) G. Gonzalez-Burgos et al.   SCHIZOPHRENIA BULLETIN

Transition to seizures in the isolated immature mouse hippocampus: a switch from dominant phasic inhibition to dominant phasic excitation

(2007) M. Derchansky et al.   JOURNAL OF PHYSIOLOGY-LONDON