Article
Biochemistry & Molecular Biology
Haruna Takeda, Yumiko Yoshimura, Masahiro Takagi, Arisa Sato, Nanako Kihara, Mohammed E. Choudhury, Hajime Yano, Junya Tanaka
Summary: Bromovalerylurea (BU) is an acyl urea derivative originally developed as a hypnotic/sedative. Recent research has shown that BU improves sepsis, Parkinson's disease, and traumatic brain injury in Wistar rat models through anti-inflammatory actions on microglia and macrophages. However, the hypnotic mechanism and characteristics of BU are poorly understood due to its long history of development.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Neurosciences
Ani Kaplanian, Michael Vinos, Irini Skaliora
Summary: Slow oscillations and their cellular counterpart, Up and Down states (UDSs), are considered as markers of cortical network organization. Inhibition mediated by GABA(B) and GABA(A) receptors plays a major role in regulating UDS activity. This study reveals for the first time age-dependent effects of GABA(B) and GABA(A) signaling on UDSs and highlights the differential subunit composition of postsynaptic GABA(A) receptors in young and adult animals. These findings provide insights into the mechanisms underlying the maturation of cortical network activity and contribute to our understanding of the development of neurodevelopmental disorders.
JOURNAL OF PHYSIOLOGY-LONDON
(2022)
Article
Neurosciences
Daisy Lin, Jinyang Liu, Alizna Florveus, Vanathi Ganesan, James E. Cottrell, Ira S. Kass
Summary: Understanding the different mechanisms associated with different anesthetic targeted receptors is crucial for determining accurate long-term outcome measures resulting from early-life anesthetic exposure. The study found that early-life exposure to sevoflurane reduced GABAergic inhibition and enhanced seizure activity later in life, while early-life exposure to ketamine did not have a significant impact on excitatory CA1 output.
Article
Neurosciences
Martin Field, Istvan P. Lukacs, Emily Hunter, Richard Stacey, Puneet Plaha, Laurent Livermore, Olaf Ansorge, Peter Somogyi
Summary: The study found that specific types of interneurons in the human neocortex, such as rosehip cells and layer 2-3 innervating cells, exhibit larger tonic GABA(A) receptor currents compared to other interneuron types, potentially allowing for selective modulation of cortical circuitry. Patient parameters like age, seizures, cancer type, and anticonvulsant treatment were also examined for their potential influence on tonic inhibitory currents in human neurons.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Silas A. Buck, M. Quincy Erickson-Oberg, Ryan W. Logan, Zachary Freyberg
Summary: Dopamine and glutamate neurotransmission play important roles in the pathophysiology of schizophrenia. However, focusing solely on neurons that release dopamine or glutamate cannot fully explain the disease. Treatment strategies should target both dopamine and glutamate signaling, as they interact extensively. Additionally, neurons that co-release dopamine and glutamate may provide a missing link in our understanding of schizophrenia pathophysiology.
MOLECULAR PSYCHIATRY
(2022)
Article
Multidisciplinary Sciences
Robert A. McCutcheon, Kirsten Brown, Matthew M. Nour, Stephen M. Smith, Mattia Veronese, Fernando Zelaya, Martin Osugo, Sameer Jauhar, William Hallett, Mitul M. Mehta, Oliver D. Howes
Summary: The study found shared information between dopamine signaling and neural activity, with patterns of striatal dopamine signaling and cortical blood flow containing shared information in healthy volunteers. The results reveal the relevance for understanding diseases where abnormalities of cortical activity and dopamine signaling coexist in neuropsychiatric illnesses.
Article
Clinical Neurology
J. Titulaer, O. Radhe, K. Danielsson, S. Dutheil, M. M. Marcus, K. Jardemark, T. H. Svensson, G. L. Snyder, M. Ericson, R. E. Davis, A. Konradsson-Geuken
Summary: Lumateperone is a novel drug approved for the treatment of schizophrenia and depressive episodes associated with bipolar depression. It simultaneously modulates key neurotransmitters and improves symptoms while enhancing prosocial behavior. The drug affects dopamine and glutamate signaling, potentially contributing to its effectiveness in improving mood-related symptoms.
EUROPEAN NEUROPSYCHOPHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Jason da Silva Castanheira, Hector Domingo Orozco Perez, Bratislav Misic, Sylvain Baillet
Summary: The authors demonstrate that just seconds of brain activity can differentiate individuals, even when recorded weeks or months apart. Utilizing fMRI data, it is possible to distinguish individuals within a cohort and predict individual traits. The study extends the concept of a neural or brain fingerprint to fast and large-scale resting-state electrophysiological dynamics.
NATURE COMMUNICATIONS
(2021)
Article
Neurosciences
Almudena Barbero-Castillo, Pedro Mateos-Aparicio, Leonardo Dalla Porta, Alessandra Camassa, Lorena Perez-Mendez, Maria V. Sanchez-Vives
Summary: This study explored the role of GABAergic inhibition in cortical complexity, finding that physiological levels of inhibition contribute to dynamical richness and spatiotemporal complexity, while decreased or increased inhibition leads to decreased cortical complexity. Using a computational model, the study demonstrated a link between excitatory/inhibitory balance and the complexity expressed by the cortical network.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Clark W. Bird, Glenna J. Chavez, Megan J. Barber, C. Fernando Valenzuela
Summary: Prenatal ethanol exposure leads to cognitive deficits in rodents through alterations in interneuron function, particularly in the retrosplenial cortex. Acute and long-term effects of ethanol on GABAergic neurotransmission in neonatal and adolescent mice were studied, revealing potential mechanisms underlying learning and memory deficits seen in ethanol-exposed mice.
SCIENTIFIC REPORTS
(2021)
Review
Neurosciences
Heiko J. Luhmann
Summary: This review article provides a brief summary of the novel technologies, challenges, current understanding, and open questions in the field of neurophysiology of the developing cerebral cortex in rodents. The use of high-density multi-electrode arrays and genetically encoded calcium indicators has allowed the recording of neuronal activity in large cortical networks, revealing surprising patterns of cortical and subcortical activity during early development. However, the functional roles of these activity patterns and their impact on cortical maturation are not yet fully understood. Future research will focus on targeted genetic manipulations and optogenetics to elucidate the function of early cortical circuits and their role in the generation of activity patterns.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Biology
Amit Kumar, Edi Barkai, Jackie Schiller
Summary: Contrary to previous beliefs, this study found that synaptic plasticity in LOT synapses is stronger and more robust than in IC synapses when receiving specific stimulation, suggesting a self-potentiating mechanism for odor information via NMDA-spikes. Additionally, association between olfactory and contextual information through STDP mechanisms provides cognitive and emotional value to odors.
Article
Multidisciplinary Sciences
Andre Steinecke, McLean M. Bolton, Hiroki Taniguchi
Summary: Interregional neuronal communication plays a crucial role in cortical circuit assembly. The cholinergic system regulates inhibitory axonal ramification in the developing neocortex by signaling through nicotinic acetylcholine receptors and T-type voltage-dependent calcium channels. Proper levels of subcortical cholinergic neuron activity are necessary for the normal development of chandelier cell axonal arbors.
Article
Neurosciences
Mengsen Zhang, Yinming Sun, Manish Saggar
Summary: The study introduces a new modeling framework to examine how functional connectivity depends on structural connectivity in the brain. The research found that cross-attractor coordination between brain regions better predicts human functional connectivity than noise-driven single-attractor dynamics. This cross-attractor coordination better accounts for the nonlinear dependency of functional connectivity on structural connectivity.
Article
Cell Biology
Weili Shi, Fan Yang, Ranran Dai, Yafei Sun, Yan Chu, Shixiu Liao, Bingtao Hao
Summary: Down syndrome is a common genetic condition characterized by intellectual disability. The m6A modification in DS brain tissue may be reduced, leading to abnormal gene expression.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Clinical Neurology
Astrid Pechmann, Max Behrens, Katharina Doernbrack, Adrian Tassoni, Sabine Stein, Sibylle Vogt, Daniela Zoeller, Gunther Bernert, Tim Hagenacker, Ulrike Schara-Schmidt, Inge Schwersenz, Maggie C. Walter, Matthias Baumann, Manuela Baumgartner, Marcus Deschauer, Astrid Eisenkoelbl, Marina Flotats-Bastardas, Andreas Hahn, Veronka Horber, Ralf A. Husain, Sabine Illsinger, Jessika Johannsen, Cornelia Koehler, Heike Koelbel, Monika Mueller, Arpad von Moers, Kurt Schlachter, Gudrun Schreiber, Oliver Schwartz, Martin Smitka, Elisabeth Steiner, Eva Stoegmann, Regina Trollmann, Katharina Vill, Claudia Weiss, Gert Wiegand, Andreas Ziegler, Hanns Lochmueller, Janbernd Kirschner
Summary: This study presents real-world evidence on the effects of nusinersen treatment in patients with early-onset spinal muscular atrophy. The findings demonstrate significant improvements in motor function, particularly in children under the age of 2. However, the improvements in bulbar and respiratory function are not equivalent to those in motor function.
Article
Genetics & Heredity
Sami Zaqout, Atef Mannaa, Oliver Klein, Angelika Krajewski, Joachim Klose, Lena Luise-Becker, Ahmed Elsabagh, Khaled Ferih, Nadine Kraemer, Ethiraj Ravindran, Konstantin Makridis, Angela M. Kaindl
Summary: Proteomic changes in the cerebral cortices of Cdk5rap2 mutant mice were studied, revealing potential protein candidates for the disease-associated phenotype reported in MCPH3.
ANNALS OF HUMAN GENETICS
(2023)
Article
Psychology, Developmental
Iryna Schommartz, Philip F. Lembcke, Francesco Pupillo, Henriette Schuetz, Nina Wald de Chamorro, Martin Bauer, Angela M. Kaindl, Claudia Buss, Yee Lee Shing
Summary: During early to middle childhood, the brain regions responsible for memory consolidation undergo significant changes. This study found that children, compared to young adults, have weaker retention of learned object-location associations in both short and long-term memory consolidation. Additionally, specific brain structures were found to be related to variations in memory retention, providing insights into the mechanisms of memory development in children.
DEVELOPMENTAL COGNITIVE NEUROSCIENCE
(2023)
Article
Biology
Lydie Burglen, Evelien Van Hoeymissen, Leila Qebibo, Magalie Barth, Newell Belnap, Felix Boschann, Christel Depienne, Katrien De Clercq, Andrew G. L. Douglas, Mark P. Fitzgerald, Nicola Foulds, Catherine Garel, Ingo Helbig, Katharina Held, Denise Horn, Annelies Janssen, Angela M. Kaindl, Vinodh Narayanan, Christina Prager, Mailys Rupin-Mas, Alexandra Afenjar, Siyuan Zhao, Vincent Th Ramaekers, Sarah M. Ruggiero, Simon Thomas, Stephanie Valence, Lionel Van Maldergem, Tibor Rohacs, Diana Rodriguez, David Dyment, Thomas Voets, Joris Vriens
Summary: TRPM3 is a plasma membrane cation channel that is sensitive to temperature and neurosteroids and is expressed in various types of cells. Rare variants in TRPM3 have been found in individuals with developmental and epileptic encephalopathy, but the connection between TRPM3 activity and neurological disorders is not well understood. In this study, we identified additional heterozygous missense variants in TRPM3 in 10 patients with a range of neurodevelopmental symptoms. These variants cause a gain-of-function phenotype, leading to increased channel activity and altered calcium levels in cells. Treatment with the TRPM3 antagonist primidone reduced the increased channel activity, suggesting that TRPM3 antagonists could be a potential therapy for these disorders.
Article
Immunology
Isabel Buenger, Konstantin L. Makridis, Jakob Kreye, Marc Nikolaus, Eva Sedlin, Tim Ullrich, Christian Hoffmann, Johannes Vincent Tromm, Helle Foverskov Rasmussen, Dragomir Milovanovic, Markus Hoeltje, Harald Pruess, Angela M. Kaindl
Summary: Maternal autoantibodies can be transmitted diaplacentally and may have deleterious effects on neurodevelopment. The presence of SYN1 autoantibodies in mothers is associated with an increased risk for intellectual disability and behavioral problems in their children. Additionally, children with SYN1 autoantibodies more frequently exhibit epilepsy, macrocephaly, and developmental delay.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Clinical Neurology
Svea Horn, Magdalena Danyel, Nina Erdmann, Felix Boschann, Cecilia Gunnarsson, Saskia Biskup, Jerome Juengling, Cornelia Potratz, Christine Prager, Angela M. Kaindl
Summary: Recently, biallelic variants in the KPTN gene have been identified in individuals with a novel syndrome called autosomal recessive intellectual developmental disorder 41 (MRT41). MRT41 is characterized by developmental delay, language development impairment, behavioral abnormalities, and epilepsy. Through exome sequencing, three different biallelic variants in KPTN were discovered in five affected individuals from three unrelated families. This research further delineates the KPTN-related syndrome, highlighting the severity of epilepsy phenotypes and treatment difficulties.
FRONTIERS IN NEUROLOGY
(2023)
Article
Clinical Neurology
Lynda El-Hassar, Ahmed Amara, Benoit Sanson, Oana Lacatus, Ahmed Amir Belhouchet, Madelon Kroneman, Kristl Claeys, Jean Philippe Plancon, Carmelo Rodolico, Guido Primiano, Francesca Trojsi, Massimiliano Filosto, Tiziana Enrica Mongini, Sara Bortolani, Mauro Monforte, Elena Carraro, Lorenzo Maggi, Federica Ricci, Vincenzo Silani, Daniele Orsucci, Alain Creange, Yann Pereon, Tanya Stojkovic, Nadine Anna Maria Elisabeth van der Beek, Antonio Toscano, Davide Pareyson, Shahram Attarian, Peter Y. K. Van den Bergh, Gauthier Remiche, Janneke G. J. Hoeijmakers, Umesh Badrising, Nicol C. Voermans, Angela M. Kaindl, Ulrike Schara-Schmidt, Benedikt Schoser, Elisabetta Gazzerro, Jana Haberlova, Stanislav Vohanka, Endre Pal, Maria Judit Molnar, Lea Leonardis, Ivailo L. Tournev, Andres Nascimento Osorio, Montse Olive, Nuria Muelas, Jorge Alonso-Perez, Francesc Pla, Marianne de Visser, Gabriele Siciliano, Sabrina Sacconi
Summary: Telemedicine has played a crucial role in providing healthcare assistance for NMD patients during the COVID-19 pandemic. However, there are limitations in its application, especially for patients with cognitive deficits or those in need of initial diagnosis. Therefore, it should be used as a complement rather than a substitute for face-to-face consultations.
JOURNAL OF NEUROMUSCULAR DISEASES
(2023)
Article
Clinical Neurology
Fabienne Kuehne, Lena-Luise Becker, Thomas Bast, Astrid Bertsche, Ingo Borggraefe, Christian Malte Bosselmann, Joerg Fahrbach, Christoph Hertzberg, Nina A. Herz, Martin Hirsch, Martin Holtkamp, Christine Janello, Gerhard Josef Kluger, Gerhard Kurlemann, Holger Lerche, Konstantin L. Makridis, Felix von Podewils, Milka Pringsheim, Susanne Schubert-Bast, Juliane Schulz, Andreas Schulze-Bonhage, David Steinbart, Bernhard J. Steinhoff, Adam Strzelczyk, Steffen Syrbe, Heike De Vries, Christiane Wagner, Johanna Wagner, Bernd Wilken, Christine Prager, Kerstin A. Klotz, Angela M. Kaindl
Summary: This retrospective multicenter study analyzed the efficacy and tolerability of CBD in 311 epilepsy patients. The results showed that CBD had a significant antiseizure effect and was well-tolerated. Approximately one third of the patients discontinued the therapy due to adverse effects or lack of efficacy. These findings suggest the potential of CBD for other epilepsy subtypes and children under 2 years old, calling for further trials.
Article
Clinical Neurology
Karen L. Oliver, Marina Trivisano, Simone A. Mandelstam, Angela De Dominicis, David I. Francis, Timothy E. Green, Alison M. Muir, Apoorva Chowdhary, Christoph Hertzberg, Klaus Goldhahn, Julia Metreau, Christine Prager, Jason Pinner, Michael Cardamone, Kenneth A. Myers, Richard J. Leventer, Gaetan Lesca, Melanie Bahlo, Michael S. Hildebrand, Heather C. Mefford, Angela M. Kaindl, Nicola Specchio, Ingrid E. Scheffer
Summary: This study analyzed the epileptology and imaging features of WWOX-DEE, and investigated genotype-phenotype correlations, particularly with regard to survival. The results showed that biallelic WWOX pathogenic variants cause an early infantile developmental and epileptic encephalopathy syndrome, with focal seizures and epileptic spasms being the most common seizure types. Patients with two null WWOX pathogenic variants have higher mortality risk.
Article
Clinical Neurology
Lena-Luise Becker, Denise Horn, Felix Boschann, Evelien Van Hoeymissen, Thomas Voets, Joris Vriens, Christine Prager, Angela M. Kaindl
Summary: DEE-SWAS is an age-dependent disease that causes cognitive decline. This study reports on two children with DEE-SWAS and developmental delay/regression, who had missense variants in the TRPM3 gene. Treatment with primidone improved their developmental regression, psychomotor development, and eliminated CSWS.
Article
Clinical Neurology
Sebastian Hoyer, Konstantin L. Makridis, Deniz A. Atalay, Ulrich-W Thomale, Christine Prager, Christian E. Elger, Angela M. Kaindl
Summary: This study examines the impact of pediatric epilepsy surgery on family burden (FB). The results show that after epilepsy surgery, patients have reduced seizures, decreased FB, and improved behavioral problems.
Article
Clinical Neurology
Ethiraj Ravindran, Gaetan Lesca, Louis Januel, Linus Goldgruber, Achim Dickmanns, Henri Margot, Angela M. Kaindl
Summary: The study reports NUP85 gene mutations in two unrelated individuals with primary autosomal recessive microcephaly (MCPH) and Seckel syndrome (SCKS) without symptoms of steroid-resistant nephrotic syndrome (SRNS). The mutations were found to result in reduced cell viability and altered structure and interactions of NUP85, further highlighting the crucial role of NUP85 in brain development and function.
FRONTIERS IN NEUROLOGY
(2023)
Review
Clinical Neurology
Lena-Luise Becker, Angela M. Kaindl
Summary: Corticosteroids have been used for the treatment of epilepsy for a long time, but their effectiveness in different types of epilepsy remains uncertain. This study conducted a systematic overview of corticosteroid regimes in childhood epilepsies and found that the duration, dosage, and protocols varied widely among studies. While there is evidence supporting the use of steroids in epileptic spasms, the overall positive effect in other epilepsy syndromes and drug-resistant epilepsies is limited. Controlled studies using steroids, especially in drug-resistant epilepsies, are urgently needed to provide new treatment options for patients.
FRONTIERS IN NEUROLOGY
(2023)
Article
Clinical Neurology
Ricki Colman, Peter Pierre, Julie Adriansjach, Kristin Crosno, Kevin K. Noguchi, Chrysanthy Ikonomidou
Summary: The study demonstrated that neonatal exposure to the antiseizure medications PbM can have long-lasting effects on behavior and cognition in nonhuman primates, with treated animals showing lower scores for environmental exploration and higher scores for locomotion and vocalizations compared with controls. Additionally, combined PbM and hypothermia resulted in lower scores for aggression and vigilance at 12 months.
ANNALS OF NEUROLOGY
(2023)
Review
Clinical Neurology
Lena-Luise Becker, Alexander Gratopp, Christine Prager, Christian E. Elger, Angela M. Kaindl
Summary: Status epilepticus is a life-threatening neurological emergency in childhood, particularly in the first 5 years of life, with high mortality and morbidity rates. Current treatments for convulsive status epilepticus in children may be delayed and inadequate. This study summarizes the current knowledge on treatment options and proposes a treatment algorithm. Benzodiazepines are recommended as first-line treatment, and for refractory status epilepticus, no superiority was found in fosphenytoin, levetiracetam, or phenobarbital. Limited data is available on third-line treatments for refractory status epilepticus lasting >30 min. The proposed algorithm aims to address treatment delay and reduce potential permanent neuronal damage.
FRONTIERS IN NEUROLOGY
(2023)