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.
Review
Psychiatry
Khaleel A. Razak, Devin K. Binder, Iryna M. Ethell
Summary: This study explored the association between autism spectrum disorders and sensory processing disorders, as well as the neural correlates of Fragile X Syndrome. Findings indicated that individuals with Fragile X Syndrome often exhibit atypical sensory processing, including auditory hypersensitivity. By analyzing Fmr1 KO mice, the study revealed the neural mechanisms underlying auditory hypersensitivity and proposed new therapeutic approaches.
FRONTIERS IN PSYCHIATRY
(2021)
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
Neurosciences
Kaleb Dee Miles, Caleb Andrew Doll
Summary: Developmental changes in ionic balance play a crucial role in neural circuit formation. The shift of GABAergic neurotransmission from depolarizing to hyperpolarizing output is induced by changes in Cl- gradients and is delayed in Fragile X syndrome (FXS) models. The absence of FMRP protein, which regulates chloride transporter expression, can significantly impact FXS phenotypes. This perspective summarizes the expression of Cl- transporters and discusses the imbalances in inhibitory neurotransmission in FXS, highlighting potential therapeutic strategies.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Psychiatry
Lisa Geertjens, Gianina Cristian, Eva Haspels, Jennifer Ramautar, Gert Jan van der Wilt, Matthijs Verhage, Hilgo Bruining
Summary: This study aims to validate the effects of bumetanide in subpopulations of neurodevelopmental disorders, validate a recently proposed treatment prediction effect methodology, and refine endpoint measurements.
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.
Review
Clinical Neurology
Ramkumar Aishworiya, Dragana Protic, Randi Hagerman
Summary: There is increasing recognition of the heterogeneity of origin of cases of autism spectrum disorder (ASD), with genetic etiology identified in 20-40% of cases. The Fragile X premutation state is a newly discovered disease state associated with various disorders, including ASD, and understanding molecular mechanisms may facilitate targeted treatments in the future.
JOURNAL OF NEUROLOGY
(2022)
Review
Cell Biology
Toshihiro Nomura
Summary: The imbalance of excitatory-inhibitory (E-I) balance has been implicated in various neurological and psychiatric diseases, including autism spectrum disorder (ASD). Fragile X syndrome (FXS) is a single-gene disorder that is the most common known cause of ASD, and deficits in inhibitory circuits in FXS tip the E-I balance towards excitation. Manipulating the activity of inhibitory interneurons can ameliorate symptoms in FXS, suggesting the potential for targeting interneurons to correct disrupted E-I balance in FXS.
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)
Article
Biochemistry & Molecular Biology
Dragana D. Protic, Ramkumar Aishworiya, Maria Jimena Salcedo-Arellano, Si Jie Tang, Jelena Milisavljevic, Filip Mitrovic, Randi J. Hagerman, Dejan B. Budimirovic
Summary: FXS is a neurodevelopmental disorder that can be improved through early diagnosis and interventions targeting behavior symptoms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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
Cell Biology
Haisheng Zhao, Xijing Mao, Cuilin Zhu, Xiaohan Zou, Fanzhen Peng, Wei Yang, Bingjin Li, Guangquan Li, Tongtong Ge, Ranji Cui
Summary: Autism spectrum disorder (ASD) is a series of neurodevelopmental diseases characterized by social communication deficits and repetitive behaviors. The dysregulation of GABAergic synaptic transmission is implicated in the pathogenesis of ASD, although the specific molecular mechanism is still unclear.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Neurosciences
Francisco Altimiras, Jose Antonio Garcia, Ismael Palacios-Garcia, Michael J. Hurley, Robert Deacon, Bernardo Gonzalez, Patricia Cogram
Summary: The study found alterations in the gut microbiome of Fragile X syndrome (FXS) mouse model, including metabolic pathways associated with autism. This suggests a potential association of the gut microbiome with FXS, opening new possibilities for exploring reliable treatments and non-invasive biomarkers.
FRONTIERS IN NEUROSCIENCE
(2021)
Review
Psychiatry
Edgard Verdura, Laura Perez-Cano, Ruben Sabido-Vera, Emre Guney, Jean-Marc Hyvelin, Lynn Durham, Baltazar Gomez-Mancilla
Summary: Fragile X syndrome (FXS) is characterized by clinical, genetic, and therapeutic response heterogeneity, emphasizing the need for precision medicine-based treatments. The high genetic and phenotypic heterogeneity in FXS poses challenges in drug development. Precision medicine approaches, by accurately stratifying patients and defining drug responder profiles, have the potential to improve clinical trial success rates and benefit a larger number of patients with neurodevelopmental disorders.
FRONTIERS IN PSYCHIATRY
(2021)
Article
Clinical Neurology
Maria Bove, Stefania Schiavone, Paolo Tucci, Vladyslav Sikora, Stefania Dimonte, Anna Laura Colia, Maria Grazia Morgese, Luigia Trabace
Summary: This study investigated whether early ketamine administration in mice could induce behavioral features that mimic typical symptoms of autism spectrum disorder (ASD). The results showed that adult mice receiving early ketamine administration exhibited increased stereotyped behaviors, social impairments, and anxiety-like behavior. Additionally, neurochemical and biomolecular analyses revealed alterations in neurotransmitters and immune activation biomarkers related to ASD in specific brain regions. These findings suggest that early ketamine administration may represent a suitable animal model for studying ASD-related symptoms.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2022)
Article
Neurosciences
Morgane Chiesa, Damien Guimond, Roman Tyzio, Alexandre Pons-Bennaceur, Natalia Lozovaya, Nail Burnashev, Diana C. Ferrari, Yehezkel Ben-Ari
Article
Neurosciences
Sebastien Roux, Ann Lohof, Yehezkel Ben-Ari, Bernard Poulain, Jean-Louis Bossu
FRONTIERS IN CELLULAR NEUROSCIENCE
(2018)
Review
Neurosciences
Yehezkel Ben-Ari
FRONTIERS IN CELLULAR NEUROSCIENCE
(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
