Article
Immunology
Samuel Fleury, Imane Boukhatem, Jessica Le Blanc, Melanie Welman, Marie Lordkipanidze
Summary: Platelets and neurons share many similarities in terms of secretory mechanisms and neurotransmitter regulation, with platelets serving as a potential peripheral biomarker for neuronal pathologies due to their high levels of brain-derived neurotrophic factor (BDNF). Despite the abundance of BDNF in platelets, discrepancies in the detection of BDNF receptors on platelets, such as TrkB and p75(NTR), suggest caution in using antibody-based assays for studying neurological disorders. Rigorous characterization of antibodies and bioassays is crucial to understanding the relationship between platelet and neuronal biology of BDNF.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Megumi Kaneko, Michael P. Stryker
Summary: This study demonstrates that recovery of visual responses to a deprived eye in mouse primary visual cortex during the critical period is dependent on the phosphorylation of the TrkB receptor for BDNF. The temporal relationship between the production of mature BDNF and the recovery of visual responses was investigated under different conditions, revealing that visual responses recover rapidly during binocular vision but more slowly during reverse occlusion. The production of mature BDNF preceded the physiological recovery in both conditions, suggesting that BDNF plays a permissive role in the growth of connections serving the deprived eye.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Ana Candalija, Thomas Scior, Hans-Richard Rackwitz, Jordan E. Ruiz-Castelan, Ygnacio Martinez-Laguna, Jose Aguilera
Summary: This study provides experimental evidence and computational models of a potential interaction between TrkB receptor domain D5 and tetanus neurotoxin (Hc-TeNT), suggesting a novel mechanism for neuroprotection and signaling pathway activation. It also highlights the competitive binding between Hc-TeNT and Brain-derived neurotrophic factor to TrkB receptors, affecting their phosphorylation and cellular uptake. Additionally, the co-localization of these molecules in neuromuscular junctions and motor neurons in vivo suggests a possible role in neuronal function.
Article
Biochemistry & Molecular Biology
Michel Engeln, Yang Song, Ramesh Chandra, Ashley La, Megan E. Fox, Brianna Evans, Makeda D. Turner, Shavin Thomas, T. Chase Francis, Ronna Hertzano, Mary Kay Lobo
Summary: The study suggests that motor stereotypies in early-onset neuropsychiatric diseases may be associated with dysregulated basal ganglia direct-pathway activity, with neurobiological mechanisms leading to direct-pathway neuron disconnectivity in stereotypy remaining poorly understood. The research uncovers phenotype-specific molecular alterations in D1-MSNs associated with morphological adaptations in mice displaying stereotypy behavior.
MOLECULAR PSYCHIATRY
(2021)
Article
Cell Biology
Zi-Ai Zhu, Yi-Yan Li, Juan Xu, Hui Xue, Xue Feng, Yong-Chuan Zhu, Zhi-Qi Xiong
Summary: CDKL5 deficiency disorder (CDD) is a severe epileptic encephalopathy caused by mutations in the CDKL5 gene. This study found that ablation of CDKL5 in forebrain glutamatergic neurons led to increased neural network activity and early-onset seizures via TrkB signaling. The researchers also discovered that targeting the TrkB pathway could potentially be an effective treatment for epilepsy in patients with CDKL5 mutations.
Article
Biochemistry & Molecular Biology
Alexandros Tsimpolis, Maria Kokkali, Aris Logothetis, Konstantinos Kalafatakis, Ioannis Charalampopoulos
Summary: Novel research studies have discovered complex interactions between glucocorticoid hormones and brain-derived neurotrophic factor, regulating crucial physiological processes in neuronal cells. This study investigated the acute effects of glucocorticoid stimulation on gene expression of BDNF and TrkB in astrocytes, revealing a biphasic response characterized by an initial rapid upregulation and subsequent downregulation of BDNF mRNA under the influence of glucocorticoid receptors. These findings demonstrate a rhythmic regulation of the neurotrophin system based on glucocorticoid levels, indicating the intricate trophic responses to temporal hormonal mechanisms in the brain microenvironment.
Article
Medicine, General & Internal
Danbi Jo, Yujeong Son, Gwangho Yoon, Juhyun Song, Oh Yoen Kim
Summary: The study revealed a negative correlation between adiposity and circulating adiponectins, while showing irregular patterns in the relationship between adiposity and circulating BDNFs. In vitro experiments demonstrated that adiponectin promotes adipocyte differentiation and browning, while BDNF attenuates these processes.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Xunsi Qin, Yue Zhao, Tianyi Zhang, Chenghong Yin, Jie Qiao, Wei Guo, Bai Lu
Summary: The agonistic antibody targeting the BDNF receptor TrkB can promote follicle development and oocyte maturation, reverse ovarian deficits and infertility in models of premature ovarian failure. The antibody activates TrkB signaling and restores the number and quality of oocytes and enhances fertility. This study identifies TrkB as a potential target for treating premature ovarian failure.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Oscar Marcelo Lazo, Giampietro Schiavo
Summary: Neurons process real-time information by encoding inputs from distal axons as a stream of endocytic organelles, called signalling endosomes, targeted to the soma. The sorting mechanism of TrkB to signalling endosomes is unknown. In this study, we identify Rab10 as critical for TrkB sorting and propagation of BDNF signalling from axon terminals to the soma, providing insights into neurodegenerative diseases.
Article
Biochemistry & Molecular Biology
Pengcheng Chu, Wei Guo, He You, Bai Lu
Summary: Through the study, it was found that Bdnf-e2 transcripts are primarily expressed in the ventromedial hypothalamus (VMH) in mice, and they regulate energy intake and satiety through the TrkB pathway. Re-expressing Bdnf-e2 transcripts in the VMH or activating VMH neurons can alleviate hyperphagia and obesity in Bdnf-e2(-/-) mice.
Article
Oncology
Yansong Liu, Zhonghua Zhang, Xuefeng Gao, Qinghua Ma, Zhiyong Yu, Shuhong Huang
Summary: Rab8A is upregulated in breast cancer tissues and promotes the proliferation and metastasis of breast cancer cells through interaction with TrkB. BDNF increases Rab8A expression by inhibiting its degradation, thereby promoting the growth of breast cancer. Inhibiting Rab8A levels could potentially inhibit the progression of breast cancer.
Article
Cardiac & Cardiovascular Systems
Alessandro Cannavo, Seungho Jun, Giuseppe Rengo, Federica Marzano, Jacopo Agrimi, Daniela Liccardo, Andrea Elia, Gizem Keceli, Giovanna G. Altobelli, Lorenzo Marcucci, Aram Megighian, Erhe Gao, Ning Feng, Kai Kammers, Nicola Ferrara, Livio Finos, Walter J. Koch, Nazareno Paolocci
Summary: This study found that loss of the brain-derived neurotrophic factor (BDNF) contributes to chronic postischemic heart failure. Activation of the TrkB receptor can restore myocardial BDNF content and improve ischemic myocardial function. Additionally, direct stimulation of the β3 adrenergic receptor or the use of β-blockers (via upregulation of β3 receptors) can prevent chronic postischemic heart failure.
CIRCULATION RESEARCH
(2023)
Article
Clinical Neurology
Annunziata Guarino, Barbara Bettegazzi, Nimra Aziz, Mario Barbieri, Daniela Bochicchio, Lucia Crippa, Pietro Marino, Maddalena Sguizzato, Marie Soukupova, Silvia Zucchini, Michele Simonato
Summary: Temporal lobe epilepsy often appears after an initial epileptogenic insult and may be preventable. This study tested the antioxidant agent 7,8-dihydroxyflavone (7,8-DHF) as an anti-epileptogenic drug and found that low-dose 7,8-DHF effectively reduced the frequency of seizures in the experimental model.
Article
Pharmacology & Pharmacy
Orhan Tansel Korkmaz
Summary: Neurodegenerative diseases are chronic and progressive diseases characterized by the loss of structure and function of neurons, leading to a decline in neural transmission. BDNF has emerged as an important regulator in synaptic plasticity, neuronal survival, and differentiation, and changes in BDNF levels and signaling pathways have been identified in neurodegenerative diseases. However, pharmacokinetic difficulties have limited the clinical use of BDNF, and the exploration of mimetic molecules that can effectively activate BDNF pathways may be a potential solution to overcome these limitations. This perspective article evaluates the efficacy of different BDNF mimetics in treating neurodegenerative diseases.
CURRENT PHARMACEUTICAL DESIGN
(2023)
Article
Cell Biology
Liu-Lin Xiong, Jie Chen, Ruo-Lan Du, Jia Liu, Yan-Jun Chen, Mohammed Al Hawwas, Xin-Fu Zhou, Ting-Hua Wang, Si-Jin Yang, Xue Bai
Summary: The study revealed that the mRNA expression levels of BDNF and its associated enzymes and receptors were upregulated in the ipsilateral hippocampus and cerebral cortex, while downregulated in the contralateral hippocampus and cerebral cortex 6 hours after neonatal hypoxic-ischemic brain damage. These findings suggest that BDNF and its processing enzymes and receptors may play crucial roles in the pathogenesis and recovery processes of neonatal hypoxic-ischemic brain damage.
NEURAL REGENERATION RESEARCH
(2021)
Article
Allergy
Aurelie Poli, Anais Oudin, Arnaud Muller, Ilaria Salvato, Andrea Scafidi, Oliver Hunewald, Olivia Domingues, Petr Nazarov, Vincent Puard, Virginie Baus, Francisco Azuaje, Gunnar Dittmar, Jacques Zimmer, Tatiana Michel, Alessandro Michelucci, Simone P. Niclou, Markus Ollert
Summary: Allergic airway inflammation delays tumor growth and improves survival in a mouse model of glioblastoma by modulating microglial gene expression and enhancing adaptive immunity.
Article
Physiology
Natalia Kriuchkova, Tilman Breiderhoff, Dominik Mueller, Duygu Elif Yilmaz, Hasan Demirci, Hoora Drewell, Dorothee Guenzel, Nina Himmerkus, Markus Bleich, Pontus B. Persson, Kerim Mutig
Summary: Perturbed calcium homeostasis in familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC) limits life expectancy. FHHNC is caused by loss-of-function mutations in CLDN16 or CLDN19 genes, leading to impaired paracellular reabsorption of divalent cations in the cortical thick ascending limb (cTAL). Furosemide, a loop diuretic, can compensate for this impairment by activating Ca2+ transport proteins in the distal nephron and collecting duct, resulting in reduced hypercalciuria.
Article
Neurosciences
Lucie Y. Li, Jakob Kreye, Malgorzata Burek, Cesar Cordero-Gomez, Paula C. Barthel, Elisa Sanchez-Sendin, Hans-Christian Kornau, Dietmar Schmitz, Madeleine Scharf, Patrick Meybohm, S. Momsen Reincke, Harald Pruess, Markus Hoeltje
Summary: This study identifies autoantibodies to brain blood vessels in patients with autoimmune encephalitis, suggesting their potential role in disrupting the blood-brain barrier.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Neurosciences
Ellen Knierim, Johannes Vogt, Michael Kintscher, Alexey Ponomarenko, Jan Baumgart, Prateep Beed, Tatiana Korotkova, Thorsten Trimbuch, Axel Panzer, Ortrud K. Steinlein, Ulrich Stephani, Andrew Escayg, Mahmoud Koko, Yuanyuan Liu, Holger Lerche, Dietmar Schmitz, Robert Nitsch, Markus Schuelke
Summary: The PLPPR4 gene encodes the PRG-1 protein, which modulates cortical excitatory transmission. Variants in the PLPPR4 gene are associated with BFNS/BFIS. The study found that partial loss-of-function of the Plppr4 gene has an impact on the development of BFNS/BFIS.
Article
Neurosciences
Kazi Atikur Rahman, Marta Orlando, Ayub Boulos, Ewa Andrzejak, Dietmar Schmitz, Noam E. Ziv, Harald Pruess, Craig C. Garner, Aleksandra Ichkova
Summary: Autoantibodies against NMDA receptors can cause internalization and loss of receptors, leading to the pathogenesis of NMDAR encephalitis. This study shows that microglia, a type of immune cells, play a role in removing the antibody-bound NMDARs, contributing to receptor and synapse loss. Mutations blocking the interaction between the antibody and microglia attenuate the loss of receptors and synapses, highlighting the critical involvement of microglia in autoimmune encephalitis.
Article
Biochemistry & Molecular Biology
Emily L. Relton, Nicolas J. Roth, Seda Yasa, Abuzar Kaleem, Guido Hermey, Christopher J. Minnis, Sara E. Mole, Tatyana Shelkovnikova, Stephane Lefrancois, Peter J. McCormick, Nicolas Locker
Summary: The assembly of membrane-less organelles called stress granules (SGs) is important for cells to respond and adapt to stress. SGs condense stalled mRNAs and proteins to modulate cellular activities and promote survival. Disassembly of SGs is crucial for cell viability, and mutations leading to persistent or aberrant SGs are associated with neurodegenerative diseases. In the case of CLN3 mutations, which cause juvenile neuronal ceroid lipofuscinosis, loss of CLN3 function disrupts SG dynamics and poses challenges for treating this childhood disease.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemical Research Methods
Antoine Lesur, Francois Bernardin, Ois Bernardin, Eric Koncina, Elisabeth Letellier, Gary Kruppa, Pierre-Olivier Schmit, Gunnar Dittmar
Summary: Blood analysis is a crucial part of clinical diagnostics, and mass spectrometry has made significant advancements in protein analysis in blood samples. The prm-PASEF method combines ion mobility as an additional separation dimension, increasing proteome coverage and allowing for shorter chromatographic gradients. An alternative method, g-dia-PASEF, is described as a less time-consuming approach.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Biology
Roberto De Filippo, Dietmar Schmitz
Summary: Hippocampal ripples are synchronous neural events critical for memory consolidation and retrieval. This study used a large dataset to analyze ripple propagation within the hippocampal formation and found that strong ripples propagate differently depending on their generation point along the hippocampal axis. The results suggest a distinctive role of the hippocampal septal pole in conditions of high-memory demand and highlight the impact of ripple generation location on neural activity across the hippocampus.
Article
Multidisciplinary Sciences
Jakob Kreye, S. Momsen Reincke, Stefan Edelburg, Lara M. Jeworowski, Hans-Christian Kornau, Jakob Trimpert, Peter Hombach, Sophia Halbe, Volker Noelle, Martin Meyer, Stefanie Kattenbach, Elisa Sanchez-Sendin, Marie L. Schmidt, Tatjana Schwarz, Ruben Rose, Andi Krumbholz, Sophie Merz, Julia M. Adler, Kathrin Eschke, Azza Abdelgawad, Dietmar Schmitz, Leif E. Sander, Uwe Janssen, Victor M. Corman, Harald Pruess
Summary: The emergence of novel viral variants of concern (VOCs) that evade preexisting antibody immunity poses a continuous challenge for developing updated therapies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, the patient-derived antibody CV38-142 was selected for preclinical development as a therapeutic due to its potency and breadth against multiple VOCs. CV38-142 demonstrated efficacy in vivo against VOC infection in a Syrian hamster model and showed favorable safety characteristics in human protein library screening and tissue cross-reactivity analysis. However, it did not neutralize the Omicron lineages BA.1 and BA.2, underscoring the need for developing broadly neutralizing variant-proof antibodies against SARS-CoV-2.
Article
Biochemical Research Methods
Daniel Perez-Hernandez, Liza Filali, Clement Thomas, Gunnar Dittma
Summary: Here, a protocol is presented to identify and quantify phosphopeptides during the dynamic formation of an immunological synapse. The steps include mixing isotope-labeled immune and target cells, stabilizing cell-to-cell conjugates by cross-linking, and isolating them by fluorescence-activated cell sorting. The protocol also involves the isolation of phosphopeptides by phosphopeptide enrichment and their measurement by mass spectrometry, followed by analysis of the data for cell-specific phosphopeptides using isotope labeling and label-free quantification.
Article
Biochemistry & Molecular Biology
S. Momsen Reincke, Niels von Wardenburg, Marie A. Homeyer, Hans-Christian Kornau, Gregorio Spagni, Lucie Y. Li, Jakob Kreye, Elisa Sanchez-Sendin, Sonja Blumenau, Dominik Stappert, Helena Radbruch, Anja E. Hauser, Annette Kuenkele, Inan Edes, Dietmar Schmitz, Harald Pruess
Summary: NMDAR-CAAR T cells selectively eliminate anti-NMDAR B cells and disease-causing autoantibodies, offering a promising new approach for the treatment of NMDAR encephalitis.
Article
Urology & Nephrology
Tobias Sieckmann, Gunnar Schley, Neslihan Oegel, Simon Kelterborn, Felix J. Boivin, Michael Faehling, Muhammad I. Ashraf, Martin Reichel, Emilia Vigolo, Andrea Hartner, Falk-Bach Lichtenberger, Tilman Breiderhoff, Felix Knauf, Christian Rosenberger, Felix Aigner, Kai Schmidt-Ott, Holger Scholz, Karin M. Kirschner
Summary: Experimental models have shown that impaired polyamine homeostasis contributes to various kidney pathologies, including ischemia-reperfusion, transplantation, rhabdomyolysis, cyclosporine treatment, arterial hypertension, diabetes, unilateral ureteral obstruction, high oxalate feeding, and adenine-induced injuries. These injuries lead to reduced expression of polyamine synthesis enzymes and increased expression of polyamine degrading enzymes, resulting in an imbalance of kidney polyamines.
KIDNEY INTERNATIONAL
(2023)
Review
Neurosciences
Alexandra Tzilivaki, John J. Tukker, Nikolaus Maier, Panayiota Poirazi, Rosanna P. Sammons, Dietmar Schmitz
Summary: This article explores the brain's ability to capture and store information, focusing on the types, plasticity, and activity patterns of interneurons in the hippocampus and their impact on memory processing.
Article
Oncology
Ernesto Gargiulo, Elodie Viry, Pablo Elias Morande, Anne Largeot, Susanne Gonder, Feng Xian, Nikolaos Ioannou, Mohaned Benzarti, Felix Bruno Kleine Borgmann, Michel Mittelbronn, Gunnar Dittmar, Petr Nazarov, Johannes Meiser, Basile Stamatopoulos, Alan G. Ramsay, Etienne Moussay, Jerome Paggetti
Summary: This study investigated the interactions between cancer cells and the microenvironment using mouse models of chronic lymphocytic leukemia (CLL). It found that small extracellular vesicles (sEVs) derived from CLL tissue contain specific miRNA and immune-checkpoint ligands, which alter the function and exhaustion of CD8+ T cells. Blocking sEV biogenesis delayed CLL pathogenesis and high expression of sEV-related genes correlated with poor outcomes in CLL patients.
BLOOD CANCER DISCOVERY
(2023)
Article
Biochemical Research Methods
Daniel Perez- Hernandez, Lorena Suarez-Artiles, Mattson S. O. Jones, Gunnar Dittmar
Summary: This article presents a protocol for systematically screening protein-protein interactions mediated by short linear motifs using the PrISMa technique, including parallelized pull down of interacting proteins, mass spectrometry identification, and a bioinformatic workflow. The method is applied to the transient interactome of the claudin protein family.
