Article
Immunology
Hui Lv, Xiao Gu, Xingyue Shan, Tailin Zhu, Bingke Ma, Hao-Tian Zhang, Victorio Bambini-Junior, Tiantian Zhang, Wei-Guang Li, Xiaoling Gao, Fei Li
Summary: By utilizing nanotechnology, the study found that bumetanide can effectively alleviate social deficits associated with autism spectrum disorder (ASD), specifically within the medial prefrontal cortex (mPFC) region. Furthermore, the therapeutic effect of bumetanide was found to be dependent on microglia targeting in the mPFC.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Provvidenza M. Abruzzo, Cristina Panisi, Marina Marini
Summary: During neuronal development, dysregulation of chloride homeostasis can lead to abnormalities in GABA signaling pathway, contributing to various neurodevelopmental disorders; chloride co-transporters play a key role in regulating chloride ion concentration, while oxidative stress and inflammation may affect their function.
Review
Psychiatry
Tiantian Wang, Ling Shan, Chunyue Miao, Zhida Xu, Feiyong Jia
Summary: The meta-analysis found that bumetanide significantly improved the severity of symptoms in children with ASD, especially in core symptoms such as social affect and restricted, repetitive behaviors. However, it did not show significant effects on sensory symptoms. Additionally, bumetanide had a significant positive impact on the overall therapeutic effect assessment in ASD patients.
FRONTIERS IN PSYCHIATRY
(2021)
Article
Neurosciences
Philip Hampel, Marie Johne, Bjoern Gailus, Alexandra Vogel, Alina Schidlitzki, Birthe Gericke, Kathrin Toellner, Wiebke Theilmann, Christopher Kaeufer, Kerstin Roemermann, Kai Kaila, Wolfgang Loescher
Summary: The study investigated the effects of NKCC1 expression on seizures and epilepsy using KO and WT mice. Results showed that while NKCC1 deficiency did not affect the induction and progression of epilepsy, it led to a more severe epileptic phenotype.
NEUROBIOLOGY OF DISEASE
(2021)
Review
Cell Biology
Yehezkel Ben-Ari, Enrico Cherubini
Summary: The GABA polarity shift is a widely accepted major discovery to understand brain development, and bumetanide has shown promising effects in clinical trials.
Article
Neurosciences
Wolfgang Loescher, Kai Kaila
Summary: Current NKCC1 inhibitors like bumetanide have limited penetration into the CNS, leading to the need for further research to develop brain-permeant compounds that are selective for NKCC1. Another challenge is to understand the effects of these drugs on different NKCC1-expressing cellular targets within and outside the brain parenchyma.
Review
Pharmacology & Pharmacy
Ben Boyarko, Sonia Podvin, Barry Greenberg, Jeremiah D. D. Momper, Yadong Huang, William H. H. Gerwick, Anne G. G. Bang, Luisa Quinti, Ana Griciuc, Doo Yeon Kim, Rudolph E. E. Tanzi, Howard H. H. Feldman, Vivian Hook, Powder Pennies Collaboration
Summary: Recent research has discovered that the drug bumetanide can reverse gene expression patterns associated with Alzheimer's disease (AD) and improve memory deficits in AD animal models. Patients exposed to bumetanide also show a lower incidence of AD by 35%-70%.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Yuan Dai, Lingli Zhang, Juehua Yu, Xin Zhou, Hua He, Yiting Ji, Kai Wang, Xiujuan Du, Xin Liu, Yun Tang, Shining Deng, Christelle Langley, Wei-Guang Li, Jun Zhang, Jianfeng Feng, Barbara J. Sahakian, Qiang Luo, Fei Li
Summary: This study conducted a randomized, double-blind, placebo-controlled trial on children aged 3-6 with autism spectrum disorder (ASD) to investigate the efficacy, safety, and neural mechanism of bumetanide. The results showed that bumetanide treatment was significantly better in reducing the severity of symptoms compared to placebo, and the clinical improvement was associated with a decrease in insular GABA levels. Further multi-center trials are needed to confirm the clinical significance of these findings.
Article
Chemistry, Multidisciplinary
Maria del Carmen Marin, Masae Konno, Hiromu Yawo, Keiichi Inoue
Summary: Microbial rhodopsins are a large family of photoreceptive membrane proteins that have diverse light-regulated functions. New subfamilies of microbial rhodopsins that transport H+ inwardly, known as light-driven inward H+ pumps, have recently been discovered. This study conducted the first functional conversion study by mutating key amino acids in a natural outward H+-pumping rhodopsin, resulting in the creation of an artificial inward H+ pump. This finding provides insights into the key processes that differentiate between outward and inward H+ pumps, and could contribute to the understanding of ion transport mechanisms in other ion-pumping proteins.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Neurosciences
Samu N. Kurki, Pavel Uvarov, Alexey S. Pospelov, Kalevi Trontti, Antje K. Huebner, Rakenduvadhana Srinivasan, Masahiko Watanabe, Iiris Hovatta, Christian A. Huebner, Kai Kaila, Mari A. Virtanen
Summary: The widely expressed Na-K-2Cl cotransporter NKCC1 has been hindered in its understanding of its roles in brain functions and disorders due to lack of reliable data on its developmental and (sub)cellular expression patterns. This study provides a well-controlled analysis of NKCC1 protein expression in different cell types of the mouse brain and reveals its high levels in oligodendrocytes, differential expression in neurons, microglia, astrocytes, developing pericytes, and progenitor cells of the dentate gyrus, and the presence of NKCC1 splice variants. These findings contribute to our understanding of NKCC1 functions in the brain and have implications for the development of neuron-targeting NKCC1-blockers.
Article
Neurosciences
Negah Rahmati, Kieran P. Normoyle, Joseph Glykys, Volodymyr Dzhala, Kyle P. Lillis, Kristopher T. Kahle, Rehan Raiyyani, Theju Jacob, Kevin J. Staley
Summary: Developmental, cellular, and subcellular variations in neuronal Cl- currents direction and GABA(A) receptor reversal potential were found in this study, indicating a heterogeneous cytoplasmic intracellular concentration of chloride in individual dendrites. Local [Cl-](i) levels in the murine hippocampus and cerebral cortex were measured using two-photon imaging, FLIM, and electrophysiological measurements, revealing stable microdomains persisting even after inhibition of cation-chloride cotransporters. These microdomains were progressively modified after inhibiting actin polymerization, demonstrating the role of immobile anions in their stability and highlighting their functional significance in modifying the impact of GABAergic inputs.
JOURNAL OF NEUROSCIENCE
(2021)
Editorial Material
Clinical Neurology
Kevin J. Staley
Summary: A recent Phase II trial showed that bumetanide is effective and safe as an adjunctive treatment for neonatal seizures. However, a larger multi-institutional trial is necessary to determine its efficacy accurately.
Article
Cell Biology
Bingke Ma, Xingyue Shan, Juehua Yu, Tailin Zhu, Ren Li, Hui Lv, Haidi Cheng, Tiantian Zhang, Lihua Wang, Feiyang Wei, Bo Meng, Xiaobing Yuan, Bing Mei, Xiao-Yong Zhang, Wei-Guang Li, Fei Li
Summary: This study identifies bidirectional dysregulation of Rac1 activity in the medial prefrontal cortex as a crucial mechanism for shared social deficits in mice. The dysregulation leads to excessive or inadequate excitability control, as well as changes in glutamate or GABA concentrations.
Article
Chemistry, Multidisciplinary
Shihao Pang, Xiaonan Sun, Zexin Yan, Chuantao Wang, Kai Ye, Shinan Ma, Linyong Zhu, Chunyan Bao
Summary: Inspired by the design criteria of heteroditopic receptors for ion-pair binding, a new strategy is described to construct a rotaxane transporter (RR[2]) for K+/Cl- co-transport. The use of a rigid axle improves the transport activity with an EC50 value of 0.58 mu M, presenting a significant step toward developing rotaxane artificial channels.
CHEMICAL COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Kiyoshi Egawa, Miho Watanabe, Hideaki Shiraishi, Daisuke Sato, Yukitoshi Takahashi, Saori Nishio, Atsuo Fukuda
Summary: Angelman syndrome is a neurodevelopmental disorder caused by loss of function of the maternally expressed UBE3A gene. Dysregulation of neuronal intracellular chloride concentration is involved in the pathophysiological mechanism of Ube3a(m-/p+) mice. Bumetanide, an NKCC1 inhibitor, shows potential therapeutic effects in restoring cognitive dysfunction and reducing seizure susceptibility in Ube3a(m-/p+) mice with Angelman syndrome.
SCIENTIFIC REPORTS
(2023)
Article
Neurosciences
Morgane Chiesa, Damien Guimond, Roman Tyzio, Alexandre Pons-Bennaceur, Natalia Lozovaya, Nail Burnashev, Diana C. Ferrari, Yehezkel Ben-Ari
Article
Multidisciplinary Sciences
N. Lozovaya, S. Eftekhari, R. Cloarec, L. A. Gouty-Colomer, A. Dufour, B. Riffault, M. Billon-Grand, A. Pons-Bennaceur, N. Oumar, N. Burnashev, Y. Ben-Ari, C. Hammond
NATURE COMMUNICATIONS
(2018)
Article
Multidisciplinary Sciences
Nouchine Hadjikhani, Jakob Asberg Johnels, Amandine Lassalle, Nicole R. Zurcher, Loyse Hippolyte, Christopher Gillberg, Eric Lemonnier, Yehezkel Ben-Ari
SCIENTIFIC REPORTS
(2018)
Article
Neurosciences
Amandine Fernandez, Camille Dumon, Damien Guimond, Roman Tyzio, Paolo Bonifazi, Natalia Lozovaya, Nail Burnashev, Diana C. Ferrari, Yehezkel Ben-Ari
Article
Multidisciplinary Sciences
R. Cloarec, B. Riffault, A. Dufour, H. Rabiei, L. -A. Gouty-Colomer, C. Dumon, D. Guimond, P. Bonifazi, S. Eftekhari, N. Lozovaya, D. C. Ferrari, Y. Ben-Ari
Article
Multidisciplinary Sciences
N. Lozovaya, R. Nardou, R. Tyzio, M. Chiesa, A. Pons-Bennaceur, S. Eftekhari, T-T Bui, M. Billon-Grand, J. Rasero, P. Bonifazi, D. Guimond, J-L Gaiarsa, D. C. Ferrari, Y. Ben-Ari
SCIENTIFIC REPORTS
(2019)
Article
Neurosciences
Morgane Chiesa, Romain Nardou, Natalia Lozovaya, Sanaz Eftekhari, Roman Tyzio, Damien Guimond, Diana C. Ferrari, Yehezkel Ben-Ari
Editorial Material
Pediatrics
Yehezkel Ben-Ari, Eric Lemonnier
Letter
Psychology, Developmental
Eric Lemonnier, Hamed Rabiei, David Makowski, Nouchine Hadjikhani, Yehezkel Ben-Ari
JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
(2021)
Review
Clinical Neurology
Yehezkel Ben-Ari, Eric Delpire
Summary: The study shows that phenobarbital and midazolam can reduce neonatal seizures following birth asphyxia, but their effectiveness is dependent on the timing of administration; in contrast, the chloride importer antagonist has no effect on reducing seizures. However, the efficacy of drugs on seizures may be influenced by recurrent seizures.
Article
Neurosciences
Morgane Chiesa, Hamed Rabiei, Baptiste Riffault, Diana Carolina Ferrari, Yehezkel Ben-Ari
Summary: The study found that cesarean section (CS) delivery in mice is associated with reduced brain volumes, particularly in preterm CS pups. Additionally, cellular activity and apoptosis were reduced in preterm CS mice but not in term CS mice, indicating that the combination of preterm birth and CS delivery impacts early-life processes.
Editorial Material
Cell Biology
Eric Delpire, Yehezkel Ben-Ari
Summary: Bumetanide, a specific NKCC1 cotransporter antagonist, shows potential in attenuating the severity of Autism Spectrum Disorders (ASD) and other neurodevelopmental or neurodegenerative disorders. However, its therapeutic efficacy may be challenged by the widespread expression of NKCC1 in various cell types. Additionally, disruptions in peripheral functions are linked to neurological sequels and increased incidence of the disorder. Therefore, a holistic approach considering both central and peripheral impacts may be beneficial in treating these disorders.
Article
Neurosciences
B. Riffault, R. Cloarec, H. Rabiei, M. Begnis, D. C. Ferrari, Yehezkel Ben-Ari
Summary: This study provides the first 3D atlases of the cholinergic and catecholaminergic systems in the mouse brain from embryonic day 12 to post-natal day 8 using tissue clearing, immunohistochemistry, lightsheet microscopy, and a multiresolution registration technique. The findings show a logarithmic scale increase of choline acetyltransferase and tyrosine hydroxylase positive neurons from E18 to P8 in several brain structures. Moreover, there are abrupt modifications in the developmental trajectory of many brain structures during the transition from E18 to P0.
Editorial Material
Neurosciences
Enrico Cherubini, Yehezkel Ben-Ari
Article
Cell Biology
Natalia Lozovaya, Yehezkel Ben-Ari, Constance Hammond
