Article
Clinical Neurology
Jun-Ying Wang, Guo-Ming Ma, Xiao-Qiang Tang, Qi-Li Shi, Ming-Can Yu, Min-Min Lou, Kai-Wen He, Wen-Yuan Wang
Summary: Wang et al. demonstrate that FUS plays a role in regulating synaptic transmission and neuronal properties in a brain region-specific manner, and suggest that the dysfunction of the vHPC-mPFC circuit caused by loss of FUS contributes to FTLD-linked behavioural disinhibition. This study sheds light on the synaptic function of FUS and its potential pathological role in frontotemporal lobar degeneration, providing insights into the development of neurological disorders.
Article
Multidisciplinary Sciences
Sadra Sadeh, Claudia Clopath
Summary: The study shows that different types of neural network structures can influence the formation and dynamics of assemblies. Networks with dominant excitatory interactions enable fast assembly formation but may lead to some degree of non-specific induction, while networks with strong excitatory-inhibitory interactions ensure that assembly formation is constrained to perturbed neurons only, albeit at a slower pace. These two regimes offer different trade-offs between speed and specificity for computational and cognitive tasks.
Article
Biochemistry & Molecular Biology
Fang-Jiao Zong, Xia Min, Yan Zhang, Yu-Ke Li, Xue-Ting Zhang, Yang Liu, Kai-Wen He
Summary: This study found diurnal changes in synaptic and neuronal activity of Parvalbumin-positive neurons (PVs) in the mouse primary visual cortex. The input and output of PVs were modulated in a time- and sleep-dependent manner, and inhibitory and excitatory synaptic transmission oscillated in opposite directions during the light/dark cycle. PV activity was regulated by visual experience and negatively correlated with the activity cycle of surrounding neurons.
Article
Clinical Neurology
Alessandra Sperandeo, Claudia Tamburini, Zoe Noakes, Daniel Cabezas de la Fuente, Francesca Keefe, Olena Petter, William Plumbly, Nicholas E. Clifton, Meng Li, Kathryn J. Peall
Summary: The study reveals that SGCE mutations lead to hyperexcitability in cortical stem cells, both at the network and single cell level. This is accompanied by longer and more complex neurite morphology, as well as disruption of synaptic adhesion molecules. The findings shed light on the pathogenesis of myoclonus dystonia and provide potential therapeutic targets.
Article
Biochemistry & Molecular Biology
Sonja Blumenstock, Elena Katharina Schulz-Trieglaff, Kerstin Voelkl, Anna-Lena Bolender, Paul Lapios, Jana Lindner, Mark S. Hipp, F. Ulrich Hartl, Rudiger Klein, Irina Dudanova
Summary: Researchers have developed reporter mice for neuronal proteostasis, revealing proteostasis decline in the aging brain and in a mouse model of tauopathy. Different types of protein aggregates have distinct effects on cellular protein quality control.
Article
Multidisciplinary Sciences
Yupu Wang, Ruiling Zhang, Sihao Huang, Parisa Tajalli Tehrani Valverde, Meike Lobb-Rabe, James Ashley, Lalanti Venkatasubramanian, Robert A. Carrillo
Summary: Neuronal death and brain dysfunction are characteristics of aging and neurodegeneration. This study demonstrates that healthy neurons can compensate for the death of their neighbors through cross-neuron plasticity in the Drosophila larval neuromuscular system. The Draper engulfment receptor and the Shark kinase are found to be essential for this compensation, and overexpression of the Draper-I isoform enhances cross-neuron plasticity. These findings provide insights into how healthy bystander neurons respond to the loss of neighboring neurons.
NATURE COMMUNICATIONS
(2023)
Article
Biology
Cosimo Prestigio, Daniele Ferrante, Antonella Marte, Alessandra Romei, Gabriele Lignani, Franco Onofri, Pierluigi Valente, Fabio Benfenati, Pietro Baldelli
Summary: The study demonstrates that REST/NRSF regulates neuronal homeostasis by downregulating glutamatergic transmission and increasing GABAergic inhibition in response to hyperactivity. This effect is specific to inhibitory-onto-excitatory neuron synapses and involves target- and area-selectivity.
Article
Neurosciences
Ewa Andrzejak, Eshed Rabinovitch, Jakob Kreye, Harald Pruss, Christian Rosenmund, Noam E. Ziv, Craig C. Garner, Frauke Ackermann
Summary: Anti-NMDA receptor encephalitis is a severe neuropsychiatric disorder associated with autoantibodies against NMDARs. This study reveals the effects of these antibodies on cortical network function, leading to hyperexcitability and disruption of stabilizing mechanisms. The antibodies selectively impair cortical inhibitory neurons, contrasting with their effects on excitatory neurons.
JOURNAL OF NEUROSCIENCE
(2022)
Review
Neurosciences
Sadra Sadeh, Claudia Clopath
Summary: Inhibitory stabilization is a crucial mechanism that enables high-gain excitatory networks to operate without leading to runaway activity, supported by experimental evidence in the brain and influencing cortical computation.
NATURE REVIEWS NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Sarah Bachmann, Jenice Linde, Michael Bell, Marc Spehr, Hans Zempel, Geraldine Zimmer-Bensch
Summary: Epigenetic mechanisms, particularly DNA methylation, play a crucial role in regulating synaptic activity in both mouse and human neurons. Inhibition of the DNA methyltransferase DNMT1 in human excitatory neurons resulted in a decrease in synaptic activity, highlighting the importance of epigenetic regulation in synaptic function in the human brain.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Xiulin Wu, Lianzhong Liu, Xing Xue, Xuhang Li, Kexin Zhao, Jiahang Zhang, Wenshi Li, Wei Yao, Shuang Ding, Chen Jia, Fan Zhu
Summary: In this study, the researchers investigated the effects of ERVWE1 on 5-HT neuronal plasticity and found that ERVWE1 enhanced HTR1B expression, thereby activating the ERK-ELK1-Arc pathway and reducing the complexity and spine density of 5-HT neurons. Furthermore, ERVWE1 reduced m6A levels through ALKBH5 demethylation. ALKBH5 mediated the observed alterations in 5-HT neuronal plasticity induced by ERVWE1. These findings suggest that ERVWE1 may contribute to aberrant synaptic plasticity in schizophrenia.
CELL AND BIOSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Dylan J. Kiltschewskij, Paul F. Harrison, Chantel Fitzsimmons, Traude H. Beilharz, Murray J. Cairns
Summary: Differentiation of neural progenitor cells into mature neuronal phenotypes relies on extensive temporospatial coordination of mRNA expression. Cleavage and polyadenylation of mRNA has regulatory capacity through the alteration of mRNA stability and modulation of miRNA function. Our findings suggest poly(A) tail length and APA function as part of a rich post-transcriptional regulatory matrix during neuronal differentiation.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Neurosciences
Jesus Cespon, Maria Concetta Pellicciari, Elias Paolo Casula, Carlo Miniussi
Summary: Understanding the relationship between cortical excitability, executive function, and underlying neural activity in healthy young and older adults may improve interventions aimed at supporting cognitive function in older adults. The study found that older adults exhibited alterations in cortical excitability, resulting in longer reaction times and impaired attentional and inhibitory control compared to young adults.
Article
Biology
V. Korzhova, P. Marinkovic, J. Rudan Njavro, P. M. Goltstein, F. Sun, S. Tahirovic, J. Herms, S. Liebscher
Summary: The study utilized in vivo two-photon calcium imaging to record the activity of cortical neurons in awake APPPS1 transgenic mice, revealing that persistent single cell aberrant neuronal activity is the cause of neuronal network pathology in cerebral amyloidosis models, which may have diagnostic and therapeutic implications for Alzheimer's disease (AD).
COMMUNICATIONS BIOLOGY
(2021)
Article
Neurosciences
Alexandros G. Kokkosis, Miguel M. Madeira, Zachary Hage, Kimonas Valais, Dimitris Koliatsis, Emran Resutov, Stella E. Tsirka
Summary: Chronic environmental stress and traumatic social experiences are risk factors for major depressive disorder and anxiety-related psychiatric disorders. Studies have shown that symptom severity is related to innate immune responses and upregulation of neuroinflammatory cytokine signaling in the brain's mood regulation areas. However, the role of microglia in modulating neuronal homeostasis in response to chronic stress has not been fully defined.
Article
Cell Biology
Agostina Di Pizio, Letizia Marvaldi, Marie-Christine Birling, Nataliya Okladnikov, Luc Dupuis, Mike Fainzilber, Ida Rishal
Summary: Size homeostasis is essential for cells, especially large cells like neurons. A motor-dependent length-sensing mechanism involving reduction in microtubule motor levels was proposed and validated in Dync1h1Loa sensory neurons. In this study, a new mouse model with a conditional deletion allele of exons 24 and 25 in Dync1h1 was described. Heterozygous mice with reduced dynein expression exhibited accelerated growth, mild impairments in motor functions, and delayed recovery from peripheral nerve injury.
JOURNAL OF CELL SCIENCE
(2023)
Article
Clinical Neurology
Florian Philipp Raber, Florian Vincent Gmeiner, Jens Dreyhaupt, Armin Wolf, Albert Christian Ludolph, Jens Ulrich Werner, Jan Kassubek, Katharina Althaus
Summary: This study aimed to investigate the feasibility, efficacy, and safety of intravenous thrombolysis (IVT) in functionally blind patients with non-arteritic central retinal artery occlusion (NA-CRAO). The results showed that early IVT therapy within 4.5 hours of symptom onset might be a potential treatment option for NA-CRAO. MRI should be performed in all patients for optimized treatment and secondary stroke prevention.
JOURNAL OF NEUROLOGY
(2023)
Editorial Material
Clinical Neurology
Luc Dupuis, Adriano Chio
Review
Oncology
Dagmar Fischer, Georg Fluegen, Paul Garcia, Nassim Ghaffari-Tabrizi-Wizsy, Laura Gribaldo, Ruby Yun-Ju Huang, Volker Rasche, Domenico Ribatti, Xavier Rousset, Marta Texeira Pinto, Jean Viallet, Yan Wang, Regine Schneider-Stock
Summary: The chorioallantoic membrane (CAM) model is a valuable alternative in vivo test system for studying various aspects of cancer. It can be used to investigate angiogenesis, tumor growth, immune escape, metastasis, and drug resistance. The CAM model is easily accessible due to its location and is a simple, fast, and low-cost tool for studying tumor pathology and treatment responses in vivo.
Article
Clinical Neurology
Matei Bolborea, Pauline Vercruysse, Tselmen Daria, Johanna C. Reiners, Najwa Ouali Alami, Simon J. Guillot, Stephane Dieterle, Jerome Sinniger, Jelena Scekic-Zahirovic, Amela Londo, Hippolyte Arcay, Marc-Antoine Goy, Claudia Nelson de Tapia, Dietmar R. Thal, Kazumoto Shibuya, Ryo Otani, Kimihito Arai, Satoshi Kuwabara, Albert C. Ludolph, Francesco Roselli, Deniz Yilmazer-Hanke, Luc Dupuis
Summary: Amyotrophic lateral sclerosis (ALS) is associated with impaired energy metabolism, including weight loss and decreased appetite. The neural mechanisms underlying metabolic impairment in ALS are not fully understood. This study found that hypothalamic atrophy occurs early in ALS patients. Loss of MCH-positive neurons was observed in mouse models of ALS, and supplementation with MCH led to weight gain and increased food intake in these mice. Moreover, pTDP-43 pathology and neurodegeneration were documented in the hypothalamus of ALS patients. These findings suggest that hypothalamic MCH loss contributes to the metabolic changes in ALS.
ACTA NEUROPATHOLOGICA
(2023)
Review
Clinical Neurology
Jeremy M. Shefner, Antonio Musaro, Shyuan T. Ngo, Christian Lunetta, Frederik J. Steyn, Richard Robitaille, Mamede De Carvalho, Seward Rutkove, Albert C. Ludolph, Luc Dupuis
Summary: Amyotrophic lateral sclerosis (ALS), a major motor neuron disease, has long been considered as primarily affecting motor neurons and neuromuscular junctions, with muscle changes being secondary. However, recent studies have shown that skeletal muscle dysfunction might contribute to muscle weakness, as well as the degeneration of neuromuscular junctions and motor neurons in ALS. This article explores the various potential roles of skeletal muscle in ALS pathophysiology and compares ALS to other motor neuron diseases, providing insights for future research and treatment.
Article
Medicine, General & Internal
Johannes Dorst, Patrick Weydt, David Brenner, Simon Witzel, Katharina Kandler, Andre Huss, Christine Herrmann, Maximilian Wiesenfarth, Antje Knehr, Kornelia Guenther, Kathrin Mueller, Jochen H. Weishaupt, Johannes Prudlo, Karin Forsberg, Peter M. Andersen, Angela Rosenbohm, Joachim Schuster, Francesco Roselli, Luc Dupuis, Benjamin Mayer, Hayrettin Tumani, Jan Kassubek, Albert C. Ludolph
Summary: The study found detectable metabolic alterations in presymptomatic ALS gene mutation carriers, suggesting the potential for early treatment and biomarker identification. These alterations precede changes in NfL levels, highlighting their importance in disease progression.
Review
Cell Biology
Laura Tzeplaeff, Sibylle Wilfling, Maria Viktoria Requardt, Meret Herdick
Summary: Finding effective therapy for ALS is challenging, as the exact cause and pathological pathway are unknown. Current approved drugs only have moderate effects and no curative options are available. Recent breakthroughs in genetic research bring hope for improved treatment, but more efforts are needed.
Review
Clinical Neurology
Albert Ludolph, Luc Dupuis, Edward Kasarskis, Frederik Steyn, Shyuan Ngo, Christopher McDermott
Summary: Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease with non-motor symptoms. Nutritional status and metabolic balance have been found to contribute to faster disease progression and earlier death. Cellular changes, including mitochondrial dysfunction, are also shown to contribute to bioenergetic failure in ALS. Modifying energy balance in ALS shows potential as a treatment option and multiple clinical trials are underway.
NATURE REVIEWS NEUROLOGY
(2023)
Article
Neurosciences
Laura Tzeplaeff, Jonathan Seguin, Stephanie Le Gras, Salim Megat, Brigitte Cosquer, Damien Plassard, Stephane Dieterle, Isabel Paiva, Gina Picchiarelli, Charles Decraene, Rafael Alcala-Vida, Jean-Christophe Cassel, Karine Merienne, Luc Dupuis, Anne-Laurence Boutillier
Summary: Mislocalization of FUS protein in the cytoplasm is associated with ALS and FTD. However, the mechanisms linking FUS mislocalization to hippocampal function and memory formation are not fully understood. Studies in mice show that mutated FUS affects the epigenetic regulation of hippocampal neurons, leading to a disruption in chromatin organization and impaired spatial memory.
PROGRESS IN NEUROBIOLOGY
(2023)
Article
Engineering, Biomedical
Dagmar Bertsche, Patrick Metze, Leonhard-Moritz Schneider, Ina Vernikouskaya, Volker Rasche
Summary: The purpose of this study is to investigate the potential benefit of motion-compensation in IGS systems. Based on patient data, the accuracy of the IGI system was assessed and it was found that motion synchronization significantly increased the accuracy. The impact of cardiac and respiratory motion on accuracy and precision was also observed.
INTERNATIONAL JOURNAL OF COMPUTER ASSISTED RADIOLOGY AND SURGERY
(2023)
Article
Clinical Neurology
Franz Marxreiter, Vera Lambrecht, Angelika Mennecke, Jannis Hanspach, Jelena Jukic, Martin Regensburger, Juergen Herrler, Alexander German, Jan Kassubek, Georg Groen, Hans-Peter Mueller, Frederik B. Laun, Arnd Doerfler, Juergen Winkler, Manuel A. Schmidt
Summary: Quantitative susceptibility mapping (QSM) on high-field MRI shows excellent diagnostic accuracy in the differential diagnosis of Parkinson's disease (PD) and multiple system atrophy (MSA). Particularly, putaminal susceptibility measures on ultra-high-field MRI can distinguish MSA patients from PD patients, allowing for an early and sensitive diagnosis of MSA.
THERAPEUTIC ADVANCES IN NEUROLOGICAL DISORDERS
(2023)
Review
Biochemistry & Molecular Biology
Anna Behler, Hans-Peter Mueller, Albert C. C. Ludolph, Jan Kassubek
Summary: Diffusion tensor imaging (DTI) can be used to visualize white matter alterations in patients with amyotrophic lateral sclerosis (ALS), and machine learning (ML) models based on DTI parameters offer new opportunities for ALS diagnosis and patient stratification. To capture the full range of neuropathological signatures, DTI can be combined with other modalities, such as T1w 3-D MRI, in ML models. Standardized DTI protocols and multi-center collaborations are needed to validate multimodal DTI biomarkers for ALS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Jan Kassubek, Fabrizio Stocchi, Ernest Balaguer Martinez, Rajesh Pahwa, William Ondo, Yi Zhang, Alyssa Bowling, Eric Pappert, Stuart Isaacson, Stacy Wu
Summary: Most patients with Parkinson's disease were able to optimize the dosage of sublingual apomorphine at home and find their optimal dosage.
THERAPEUTIC ADVANCES IN NEUROLOGICAL DISORDERS
(2023)
Article
Neuroimaging
Maximilian Wiesenfarth, Hans-Juergen Huppertz, Johannes Dorst, Dorothee Lule, Albert C. Ludolph, Hans-Peter Mueller, Jan Kassubek
Summary: This study explores the MRI characteristics of C9orf72-associated ALS and finds significant alterations in both white matter and gray matter in the early stages of the disease.
NEUROIMAGE-CLINICAL
(2023)