Article
Neurosciences
Enric Vidal, Manuel A. Sanchez-Martin, Hasier Erana, Sonia Perez Lazaro, Miguel A. Perez-Castro, Alicia Otero, Jorge M. Charco, Belen Marin, Rafael Lopez-Moreno, Carlos M. Diaz-Dominguez, Marivi Geijo, Montserrat Ordonez, Guillermo Cantero, Michele di Bari, Nuria L. Lorenzo, Laura Pirisinu, Claudia d'Agostino, Juan Maria Torres, Vincent Beringue, Glenn Telling, Juan J. Badiola, Marti Pumarola, Rosa Bolea, Romolo Nonno, Jesus R. Requena, Joaquin Castilla
Summary: Atypical Scrapie is considered a spontaneous idiopathic prion disease in small ruminants, and unlike classical scrapie, its occurrence and control strategies may affect its transmissibility.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Virology
Lise Lamoureux, Babu Sajesh, Jessy A. Slota, Sarah J. Medina, Matthew Mayor, Kathy L. Frost, Bryce Warner, Kathy Manguiat, Heidi Wood, Darwyn Kobasa, Stephanie A. Booth
Summary: Neurological syndromes associated with COVID-19 suggest an effect of the virus on neuronal function, but the direct infection of SARS-CoV-2 in the brain remains under debate. In this study, using brain slice culture, researchers found that while some glial cells were infected, there was no evidence of viral infection or replication in neurons. These findings support previous clinical studies on neurological involvement in COVID-19 patients.
Review
Biochemistry & Molecular Biology
Lin He, Chuxia Deng
Summary: Organotypic tissue slice culture has numerous advantages in anticancer drug development, including the preservation of cell repertoire, quick assessment of therapeutic efficacy, and the ability to select personalized treatment regimens. It is expected to become a potent platform for individualized drug screening.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Dhwani S. Korde, Christian Humpel
Summary: This study investigates the spreading of P301S aggregated tau in the brain using organotypic slice cultures and collagen hydrogels as a protein delivery system. The results show that P301S aggregated tau spreads to different areas of the brain in a time-dependent manner, and this spreading is interrupted when the neuroanatomical pathways are lesioned. The study provides a novel experimental approach to investigate tau pathology.
Article
Biology
Yingjun Liu, Assunta Senatore, Silvia Sorce, Mario Nuvolone, Jingjing Guo, Zeynep H. Gumus, Adriano Aguzzi
Summary: Cultured brain slices from mice upregulate senescence-associated genes and reproduce transcriptional characteristics of aged brains. Prions accelerate brain aging. This study establishes an innovative model system for studying brain aging.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Maria Velasco-Estevez, Nina Koch, Ilona Klejbor, Stephane Laurent, Kumlesh K. Dev, Andrzej Szutowicz, Andreas W. Sailer, Aleksandra Rutkowska
Summary: The EBI2 receptor plays a crucial role in regulating immune cells and astrocytes in the CNS. It is implicated in diseases like multiple sclerosis, where its expression is increased in immune cells. Studies showed that EBI2 is present in OPCs and plays a role in remyelination, making it a potential target for therapeutic approaches in demyelinating diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Engineering, Biomedical
Buket Ucar, Janko Kajtez, Bettina M. Foidl, Dimitri Eigel, Carsten Werner, Katherine R. Long, Jenny Emneus, Joelle Bizeau, Mihai Lomora, Abhay Pandit, Ben Newland, Christian Humpel
Summary: This study evaluated the potential of different biomaterials in reconstructing the nigrostriatal pathway. Various techniques were employed to regenerate nerve fiber growth in organotypic brain slices, highlighting the advantages and disadvantages of different technologies for neuronal regeneration strategies. The results provide a general overview for future regenerative strategies and tissue engineering applications.
ACTA BIOMATERIALIA
(2021)
Article
Biochemistry & Molecular Biology
Urszula Hohmann, Chalid Ghadban, Tim Hohmann, Joshua Kleine, Miriam Schmidt, Christian Scheller, Christian Strauss, Faramarz Dehghani
Summary: During injuries in the central nervous system, nimodipine, a lipophilic L-type calcium channel blocking agent, has neuroprotective effects on neurons and affects the survival of glia cells. The protective actions of nimodipine are time-dependent.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
James M. McCarthy, Jasmeet Virdee, Jessica Brown, Daniel Ursu, Zeshan Ahmed, Annalisa Cavallini, Hugh N. Nuthall
Summary: Intracellular tau inclusions are a hallmark of several neurodegenerative diseases, and recent studies have shown that tau aggregates can propagate to neighboring cells, leading to further tau aggregation. The ex vivo system using organotypic hippocampal slice cultures (OHCs) provides a model for studying this phenomenon and assessing potential therapeutic approaches.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Claudia A. Valente, Francisco J. Meda, Mafalda Carvalho, Ana M. Sebastiao
Summary: Organotypic slice cultures are valuable tools for modeling brain disorders and assessing the neuroprotective and therapeutic potential of drugs. Hippocampal and rhinal cortex-hippocampus slices are suitable for studying the mechanisms and progression of epileptogenesis.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2021)
Article
Neurosciences
Harvey K. Chong, Ziang Ma, Kendrew Ka Chuon Wong, Andrew Morokoff, Chris French
Summary: This study developed a technique that successfully reproduced tumour-associated epilepsy by implanting aggressive brain tumours into normal rat organotypic brain tissue. The technique allows for real-time imaging of tumour growth and invasion, as well as analysis of microvolume fluid sampling in different regions. It provides a versatile preparation for the study of major clinical problems of tumour-associated epilepsy.
Article
Neurosciences
Nevin Varghese, Nicolas E. Amelinez-Robles, Barclay Morrison III
Summary: In this study, the effects of blast-induced traumatic brain injury (bTBI) on the hippocampal network of rat organotypic hippocampal slice cultures (OHSCs) were investigated. The results showed reduced connectivity and clustering coefficients in the hippocampal network following bTBI, along with decreased expression of alpha 1 and alpha 5 GABAA receptor subunits. Treatment with the histone deacetylase inhibitor suberanilohydroxamic acid (SAHA) restored the alpha 1 subunit and attenuated deficits in network measures. These findings suggest that GABAA receptors may play a role in neuronal network changes and could be targeted for therapeutic intervention in bTBI-induced neurological symptoms.
EXPERIMENTAL NEUROLOGY
(2023)
Article
Multidisciplinary Sciences
Amy McCaughey-Chapman, Bronwen Connor
Summary: Organotypic brain slice cultures provide a 3-dimensional system for studying neurological diseases. By treating rat sagittal organotypic slices with AMPA or quinolinic acid (QA), researchers have developed ex vivo excitotoxic lesion models that mimic the in vivo process. This slice culture platform allows for long-term cellular studies and provides a valuable tool in understanding excitotoxicity and developing therapeutic strategies.
Article
Neurosciences
Ari Ogaki, Yuji Ikegaya, Ryuta Koyama
Summary: Researchers have developed a method to efficiently transplant human induced pluripotent stem cell-derived microglia (hiPSC-MG) into mouse hippocampal slice cultures, achieving a high replacement rate. The transplanted microglia changed their morphology and phagocytosed cell debris when neuronal death was induced. This method provides a useful ex vivo tool for evaluating the properties of hiPSC-MG.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Clinical Neurology
Serge Moudio, Fredrik Rodin, Nazira Jamal Albargothy, Urban Karlsson, Juan F. Reyes, Martin Hallbeck
Summary: This study utilized an organotypic brain slice culture model to investigate the formation of α-synuclein aggregates, demonstrating that this ex vivo model can recapitulate the molecular features of PD and provide insights into the cumulative effects of α-synuclein in a complex environment.
FRONTIERS IN NEUROLOGY
(2022)
Article
Multidisciplinary Sciences
Anna Henzi, Adriano Aguzzi
Summary: The study found that PrP is not essential for peripheral nerve repair processes, and Adgrg6 may sustain its function in peripheral nerve repair independently of its activation by PrP.
Article
Allergy
Carlo Cervia, Jakob Nilsson, Yves Zurbuchen, Alan Valaperti, Jens Schreiner, Aline Wolfensberger, Miro E. Raeber, Sarah Adamo, Sebastian Weigang, Marc Emmenegger, Sara Hasler, Philipp P. Bosshard, Elena De Cecco, Esther Baechli, Alain Rudiger, Melina Stuessi-Helbling, Lars C. Huber, Annelies S. Zinkernagel, Dominik J. Schaer, Adriano Aguzzi, Georg Kochs, Ulrike Held, Elsbeth Probst-Mueller, Silvana K. Rampini, Onur Boyman
Summary: The study found that severe COVID-19 patients experienced a significant increase in SARS-CoV-2 antibody titers after symptom onset, especially with high IgA titers, while mild cases may exhibit transient production of SARS-CoV-2-specific antibodies. Interestingly, some healthcare workers with negative serum antibody titers showed SARS-CoV-2-specific IgA in mucosal fluids with virus-neutralizing capacity in some cases.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Orsolya Toeroek, Bettina Schreiner, Johanna Schaffenrath, Hsing-Chuan Tsai, Upasana Maheshwari, Sebastian A. Stifter, Christina Welsh, Ana Amorim, Sucheta Sridhar, Sebastian G. Utz, Wiebke Mildenberger, Sina Nassiri, Mauro Delorenzi, Adriano Aguzzi, May H. Han, Melanie Greter, Burkhard Becher, Annika Keller
Summary: Pericytes regulate leukocyte infiltration in the adult central nervous system and play a role in neuroinflammation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Medicine, Research & Experimental
Asvin K. K. Lakkaraju, Karl Frontzek, Emina Lemes, Uli Herrmann, Marco Losa, Rajlakshmi Marpakwar, Adriano Aguzzi
Summary: This study found that prion infection and prion-mimetic antibodies deplete PIKfyve, a phosphoinositide kinase controlling endolysosomal maturation, leading to endolysosomal hypertrophy and activation of lysosomal enzymes. This depletion of PIKfyve is mediated by acyltransferases zDHHC9 and zDHHC21, whose topology is disturbed by prion infection, resulting in vacuolation in prion diseases. Restoring PIKfyve levels through different methods can suppress prion-induced vacuolation and restore lysosomal homeostasis.
EMBO MOLECULAR MEDICINE
(2021)
Article
Cell Biology
Caihong Zhu, Adriano Aguzzi
Summary: Prion diseases are neurodegenerative disorders caused by the abnormal conformational conversion of cellular prion protein. The phenomenon of prion-like spread has also been observed in other disease-associated proteins, such as Aβ, tau, and α-synuclein. Prion protein may play a role in the pathogenesis of a broad spectrum of neurodegenerative conditions, including Alzheimer's and Parkinson's disease.
JOURNAL OF CELL SCIENCE
(2021)
Article
Cell Biology
Eleanna Kara, Alessandro Crimi, Anne Wiedmer, Marc Emmenegger, Claudia Manzoni, Sara Bandres-Ciga, Karishma D'Sa, Regina H. Reynolds, Juan A. Botia, Marco Losa, Veronika Lysenko, Manfredi Carta, Daniel Heinzer, Merve Avar, Andra Chincisan, Cornelis Blauwendraat, Sonia Garcia-Ruiz, Daniel Pease, Lorene Mottier, Alessandra Carrella, Dezirae Beck-Schneider, Andreia D. Magalhaes, Caroline Aemisegger, Alexandre P. A. Theocharides, Zhanyun Fan, Jordan D. Marks, Sarah C. Hopp, Andrey Y. Abramov, Patrick A. Lewis, Mina Ryten, John Hardy, Bradley T. Hyman, Adriano Aguzzi
Summary: Through a genome-wide siRNA screen, researchers identified 38 genes that regulate the cell-to-cell transfer of alpha-synuclein, including the candidate gene ITGA8 identified in a recent PD GWAS. Weighted gene co-expression network analysis and weighted protein-protein network interaction analysis revealed that these genes cluster with known PD genes more frequently than expected by random chance, expanding our understanding of the mechanism of alpha-synuclein spread.
Article
Microbiology
Razieh Kamali-Jamil, Ester Vazquez-Fernandez, Brian Tancowny, Vineet Rathod, Sara Amidian, Xiongyao Wang, Xinli Tang, Andrew Fang, Assunta Senatore, Simone Hornemann, Sandor Dudas, Adriano Aguzzi, Howard S. Young, Holger Wille
Summary: Bovine spongiform encephalopathy (BSE), commonly known as mad cow disease, is a fatal neurodegenerative disease in cattle caused by misfolded PrPSc proteins. This study focused on L-type BSE prions, one of the three prion variants responsible for the disease, and analyzed their structural characteristics using electron microscopy. The results revealed the presence of two classes of amyloid fibrils in L-type BSE prions, with one-protofilament fibrils being more abundant compared to two-protofilament fibrils. Additionally, immunogold labeling confirmed the presence of specific PrP epitopes in the fibrils, supporting the proposed four-rung beta-solenoid model for the infectious PrPSc structure.
Article
Clinical Neurology
Asvin K. K. Lakkaraju, Silvia Sorce, Assunta Senatore, Mario Nuvolone, Jingjing Guo, Petra Schwarz, Rita Moos, Pawel Pelczar, Adriano Aguzzi
Summary: Prion infections cause derangement in glial cells but not in neurons. Expressing PrP(C) selectively in neurons and astrocytes of mice, we found that prion accumulation and disease occurred in neuron-restricted expression, while astrocyte-restricted expression did not lead to clinical disease or inflammation. This suggests a nonautonomous mechanism in which prion-infected neurons instruct astrocytes and microglia to drive neural dysfunction.
Article
Clinical Neurology
Alejandro N. Santos, Laurel Rauschenbach, Dino Saban, Bixia Chen, Marvin Darkwah Oppong, Annika Herten, Hanah Hadice Gull, Christoph Riess, Cornelius Deuschl, Boerge Schmidt, Ramazan Jabbarli, Karsten H. Wrede, Yuan Zhu, Benedikt Frank, Ulrich Sure, Philipp Dammann
Summary: This study analyzed and compared the natural course of confirmed familial cerebral cavernous malformation (FCCM), assumed FCCM, and non-familial multiple cerebral cavernous malformation (CCM) disease over a 5-year period. The results showed that FCCM patients with intracerebral hemorrhage (ICH) at diagnosis are prone to develop rebleeding. During the 5-year follow-up, FCCM patients and patients with sporadic multiple CCM have a similar susceptibility to (re)hemorrhage.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Clinical Neurology
Annika Herten, Dino Saban, Alejandro N. Santos, Bixia Chen, Marvin Darkwah Oppong, Laurel Rauschenbach, Ramazan Jabbarli, Karsten Wrede, Ulrike Bingel, Daniel Mueller, Dagny Holle-Lee, Boerge Schmidt, Yan Li, Ulrich Sure, Philipp Dammann
Summary: This study assessed the occurrence and significance of postoperative neuropathic pain in patients with surgically treated brainstem cavernous malformations. It was found that 8% of patients suffered from NP after surgery, impacting their health-related quality of life and life satisfaction.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Clinical Neurology
Alejandro N. Santos, Laurel Rauschenbach, Dino Saban, Bixia Chen, Annika Herten, Thiemo Florin Dinger, Yan Li, Stephan Tippelt, Adela Della Marina, Christian Dohna-Schwake, Boerge Schmidt, Ramazan Jabbarli, Karsten H. Wrede, Ulrich Sure, Philipp Dammann
Summary: This study investigated the natural course of cerebral cavernous malformations (CCM) in pediatric patients, highlighting a higher risk of intracerebral hemorrhage (ICH) in children with brain stem CCM and familial history of CCM. Over a 5-year follow-up, untreated pediatric patients had a similar risk of (re)hemorrhage compared to adults, with an increased probability over time, especially in cases with ICH or brain stem localization.
Article
Microbiology
Marc Emmenegger, Sreedhar Saseendran F. Kumar, Vishalini J. Emmenegger, Tomas J. Malinauskas, Thomas Buettner, Laura Rose, Peter Schierack, Martin B. Sprinzl, Clemens Sommer, Karl B. Lackner, Adriano Aguzzi, Dirk B. Roggenbuck, Katrin B. M. Frauenknecht
Summary: SARS-CoV-2 infection can lead to diverse symptoms, with some patients developing hypercoagulation and autoantibody responses. Research has shown that infection with SARS-CoV-2 can result in the production of autoantibodies, particularly IgM antibodies targeting coagulation proteins. Further investigation is needed to explore the relationship between SARS-CoV-2 infection, autoantibody production, and disease severity.
Article
Biology
Yingjun Liu, Assunta Senatore, Silvia Sorce, Mario Nuvolone, Jingjing Guo, Zeynep H. Gumus, Adriano Aguzzi
Summary: Cultured brain slices from mice upregulate senescence-associated genes and reproduce transcriptional characteristics of aged brains. Prions accelerate brain aging. This study establishes an innovative model system for studying brain aging.
COMMUNICATIONS BIOLOGY
(2022)
Correction
Biology
Yingjun Liu, Assunta Senatore, Silvia Sorce, Mario Nuvolone, Jingjing Guo, Zeynep H. Gumus, Adriano Aguzzi
COMMUNICATIONS BIOLOGY
(2022)
Article
Clinical Neurology
Regina R. Reimann, Martina Puzio, Antonella Rosati, Marc Emmenegger, Bernard L. Schneider, Pamela Valdes, Danzhi Huang, Amedeo Caflisch, Adriano Aguzzi
Summary: The cellular prion protein PrPC mediates neurotoxicity of prions and protein aggregates, but the mechanisms are not well understood. Antibody-derived ligands against PrPC induce neurotoxicity through hydrogen bonding and suppressing this bond prolongs the lives of prion-infected mice, suggesting convergent pathways. A study found that the toxic effects of these ligands require a specific amino acid residue within PrPC, which could be a potential target for preventing prion-related neurodegeneration.