Article
Neurosciences
Takahiro Fujimoto, Kirsten Stam, Takeshi Yaoi, Kenta Nakano, Tetsuya Arai, Tadashi Okamura, Kyoko Itoh
Summary: This study aimed to investigate the expression profile of Dp71 in the cerebellum and found its presence in glial cells, Bergmann glial cells, and astrocytes, while Dp427 was exclusively expressed in inhibitory postsynapses within cerebellar Purkinje cells. Additionally, the study revealed biochemical associations of Dp71 with AQP4 and Kir4.1 in both the cerebellum and cerebrum, and partial co-localization of Dp71 with AQP4 and Kir4.1 in glial cells. The results suggest that different cell types in the cerebellum express different dystrophin molecular complexes, which may play a role in pathological and physiological processes through the regulation of water/ion channels and inhibitory postsynapses.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Karthik Subramanian Krishnan, Brian Billups
Summary: D-serine is a crucial signaling molecule that works in tandem with glutamate to activate NMDA receptors. Astrocytes are hypothesized to control extracellular levels of D-serine by removing it from the synaptic space, suggesting that astrocytes play a significant role in regulating synaptic plasticity and memory.
Article
Neurosciences
Vasiliki Tellios, Matthew J. E. Maksoud, Wei-Yang Lu
Summary: This study is the first to characterize BG morphology and GLAST expression during development in nNOS(-/-) mice using immunohistochemistry and western blotting. The results showed that BG in nNOS(-/-) mice exhibited abnormal morphology and decreased GLAST expression compared with wildtype (WT) mice across postnatal development. It was also found that nNOS/NO signaling regulates BG development through a PKG-mediated mechanism.
Article
Neurosciences
Angelica Salinas-Birt, Xiangyu Zhu, Eunice Y. Lim, Aryana J. Cruz J. Santory, Liang Ye, Martin Paukert
Summary: Behavioral state plays an important role in astroglia Ca2+ signaling, with locomotion-induced vigilance triggering norepinephrine-dependent Ca2+ elevations. The speed of locomotion has little effect on Ca2+ signals, but prolonged locomotion events result in steady-state Ca2+ elevation. Coordinated activity among noradrenergic terminals determines Bergmann glia Ca2+ activity.
Article
Biochemistry & Molecular Biology
America Vera-Montecinos, Jordi Galiano-Landeira, Monica Roldan, Francisco Vidal-Domenech, Enrique Claro, Belen Ramos
Summary: METTL7A is mainly located in the endoplasmic reticulum and lipid droplets, with limited cellular expression in the brain. Reduced protein levels of METTL7A have been found in schizophrenia. Our study shows that METTL7A is highly expressed in Bergmann glia and has contacts with Purkinje neurons. The localization of METTL7A may play a role in maintaining cerebellar homeostasis and modulating cerebellar circuits.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Shaoxuan Chen, Kunkun Zhang, Boxin Zhang, Mengyun Jiang, Xue Zhang, Yi Guo, Yingying Yu, Tianyu Qin, Hongda Li, Qiang Chen, Zhiyu Cai, Site Luo, Yi Huang, Jin Hu, Wei Mo
Summary: The study reveals that the transcriptomic landscapes of Bergmann glia offer insights into the mechanism by which these cells are deeply integrated into the cerebellar neural network.
Article
Immunology
Chandrakanth Reddy Edamakanti, Vishwa Mohan, Puneet Opal
Summary: Using human SCA autopsy samples, researchers discovered inflammatory JNK-dependent c-Jun phosphorylation in Bergmann glia, and inhibiting the JNK pathway reduced Bergmann glia inflammation and improved the SCA1 phenotype both behaviorally and pathologically, suggesting a causal role for Bergmann glia inflammation in SCA1 and a potential therapeutic strategy.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Neurosciences
Shelanah Salih, Zubair Ahmed Nizamudeen, Nigel De Melo, Lisa Chakrabarti, Virginie Sottile
Summary: Recent observations suggest that Bergmann glia in the cerebellum may play a role in tissue repair due to their expression of neural stem cell markers, although the physiological relevance of this overlap remains unclear in the absence of established in vivo evidence of tissue regeneration in the adult cerebellum.
EXPERIMENTAL NEUROLOGY
(2022)
Article
Neurosciences
Ella Borgenheimer, Katherine Hamel, Carrie Sheeler, Francisco Labrada Moncada, Kaelin Sbrocco, Ying Zhang, Marija Cvetanovic
Summary: In the early stages of SCA1 in mice, there were no changes in the proportions of neurons and glial cells in the cerebellum, but Bergmann glia, velate astrocytes, and oligodendrocytes showed profound non-cell autonomous and potentially neuroprotective reactive gene and pathway alterations in response to Purkinje cell dysfunction.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Neurosciences
Carmen Nanclares, Jose Antonio Noriega-Prieto, Francisco E. Labrada-Moncada, Marija Cvetanovic, Alfonso Araque, Paulo Kofuji
Summary: Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disease characterized by progressive cerebellar ataxia. This study found that the intrinsic electrical properties of Purkinje cells (PCs) in SCA1 mice were altered, and these alterations were associated with the hyperexcitability of Bergmann glia (BG). Preventing BG hyperexcitability in SCA1 mice restored the normal function of PCs.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Xia Li, Romain Helleringer, Lora L. Martucci, Glenn Dallerac, Jose-Manuel Cancela, Micaela Galante
Summary: Cerebral ischemia, which is caused by a reduction or interruption in blood supply to the brain, leads to deprivation of oxygen and glucose. The consequences of cerebral ischemia include loss of metabolic ATP, accumulation of K+ and glutamate in the extracellular space, electrolyte imbalance, and brain edema formation. This study focuses on the neuroprotective role of hypothermia in a mouse cerebellar slice model of ischemia, and found that lowering the temperature delays the increase of K+ and tissue swelling. In addition, hypothermia hinders the morphological changes and membrane depolarizations of Bergmann glial cells, suggesting that it reduces harmful homeostatic changes in cerebellar ischemia.
Article
Neurosciences
Vanessa L. Hull, Yan Wang, Travis Burns, Sarah Sternbach, Shuaishuai Gong, Jennifer McDonough, Fuzheng Guo, Laura N. Borodinsky, David Pleasure
Summary: Canavan disease is a pediatric leukodystrophy caused by mutations in the ASPA gene, resulting in a deficiency of the enzyme aspartoacylase. This leads to increased levels of N-acetyl-L-aspartate (NAA) in the brain and various neurological symptoms. In a mouse model of Canavan disease, researchers found that Bergmann glia (BG) exhibited significant morphological alterations and dysfunction, which preceded cerebellar degeneration. However, treatment with an antisense oligonucleotide targeting Nat8l, which reduces NAA production, was able to repair the BG and improve motor function. This suggests that restoring BG integrity may be a potential therapeutic strategy for Canavan disease.
Article
Endocrinology & Metabolism
Anthony D. Bird, Emily R. Frost, Stefan Bagheri-Fam, Brittany M. Croft, Janelle M. Ryan, Liang Zhao, Peter Koopman, Vincent R. Harley
Summary: During sex determination in mice, FGFR2c is involved in testis development while FOXL2 and WNT4/RSPO1 pathways drive ovarian development. The role of FGFR2 in the ovary and its requirement in the testis after sex determination are not clear.
Article
Multidisciplinary Sciences
Nagham Khouri-Farah, Qiuxia Guo, Kerry Morgan, Jihye Shin, James Y. H. Li
Summary: Recent studies using single-cell RNA-sequencing have identified cellular heterogeneity in the developing mammalian cerebellum, but the regulatory logic behind this diversity remains unclear. Researchers integrated single-cell RNA and ATAC analyses to understand the developmental trajectories of cerebellar progenitors and identified potential regulatory elements controlling cell state transitions. Using gene regulatory network analysis, they uncovered the molecular control of a specific progenitor zone and demonstrated its association with a common cerebellar birth defect in humans.
Article
Neurosciences
Bumwhee Lee, Laura Beuhler, Hye Young Lee
Summary: The study revealed a reduction in the number of primary cilia and Sonic hedgehog (Shh) signaling in cerebellar Bergmann glia of Fmr1 KO mice, leading to reduced Granule Neuron Precursor (GNP) proliferation and thickness of the External Germinal Layer (EGL). This suggests that deficits in primary cilia of Bergmann glia may contribute to cerebellar developmental phenotypes in Fragile X Syndrome (FXS).
Article
Multidisciplinary Sciences
Ngoc Tung Tran, Eric Danner, Xun Li, Robin Graf, Mikhail Lebedin, Kathrin de la Rosa, Ralf Kuehn, Klaus Rajewsky, Van Trung Chu
Summary: This study establishes a spacer-nick gene correction approach that combines Cas9D10A nickase with a pair of PAM-out sgRNAs, resulting in efficient gene correction with reduced off-target mutations. The results suggest that this approach provides improved safety and suitability for gene therapy.
Article
Oncology
Ulrike Pfohl, Juergen Loskutov, Sanum Bashir, Ralf Kuhn, Patrick Herter, Markus Templin, Soulafa Mamlouk, Sergei Belanov, Michael Linnebacher, Florian Buertin, Marcus Vetter, Christoph Reinhard, Lena Wedeken, Christian R. A. Regenbrecht
Summary: This research investigated the impact of loss-of-function of the SMAD4 gene on the sensitivity to MEK inhibitors in colorectal cancer using CRISPR technology. It identified a mutation signature related to the TGF-beta/BMP signaling pathway and found a gene signature (SFAB) that can predict sensitivity to MEK inhibitors.
Article
Veterinary Sciences
Sabine M. Hoelter, Sara Wells, Vootele Voikar
Summary: The key goal in biomedical research is to understand the causes of diseases and develop strategies for prevention and effective therapies. Concerns have been raised about the reproducibility and translational validity of preclinical research in animal models. Automated behavior monitoring in the animal's home cage is a promising solution to improve the validity and translatability of animal studies.
LABORATORY ANIMALS
(2023)
Article
Biology
Justine Chee, Louise Lanoue, Dave L. Clary, Kendall Higgins, Lynette Bower, Ann Flenniken, Ruolin Guo, David Adams, Fatima Bosch, Robert E. Braun, Steve D. M. Brown, H. -J. Genie Chin, Mary Dickinson, Chih-Wei Hsu, Michael Dobbie, Xiang Gao, Sanjeev Galande, Anne Grobler, Jason Heaney, Yann Herault, Martin Hrabe de Angelis, Fabio Mammano, Lauryl M. J. Nutter, Helen Parkinson, Chuan Qin, Toshi Shiroishi, Radislav Sedlacek, J-K Seong, Ying Xu, Brian Brooks, Colin McKerlie, K. C. Kent Lloyd, Henrik Westerberg, Ala Moshiri
Summary: This study identified new genes and pathways associated with eye development through screening of mouse genes. These findings provide insights into the molecular and cellular mechanisms of eye development and could potentially contribute to the diagnosis and treatment of congenital blinding diseases.
Article
Medicine, General & Internal
Vibeke Fosse, Emanuela Oldoni, Florence Bietrix, Alfredo Budillon, Evangelos P. Daskalopoulos, Maddalena Fratelli, Bjoern Gerlach, Peter M. A. Groenen, Sabine M. Holter, Julia M. L. Menon, Ali Mobasheri, Nikki Osborne, Merel Ritskes-Hoitinga, Bettina Ryll, Elmar Schmitt, Anton Ussi, Antonio L. Andreu, Emmet McCormack
Summary: Personalized medicine aims to provide tailor-made prevention and treatment strategies for specific groups, but there are challenges in clinical relevance and model validity. Researchers have developed a set of recommendations to improve the robustness of preclinical methods in translational research for personalized medicine through literature review, expert discussions, and consensus meetings.
Article
Biochemistry & Molecular Biology
Lillian Garrett, Dietrich Truembach, Nadine Spielmann, Wolfgang Wurst, Helmut Fuchs, Valerie Gailus-Durner, Martin Hrabe De Angelis, Sabine M. Hoelter
Summary: Neuropsychiatric diseases represent a significant global disease burden and require innovative approaches for pathogenic understanding, biomarker identification, and therapeutic strategies. The malfunction of the heart/brain axis, particularly through the autonomic nervous system and brain central autonomic network interaction, plays a crucial role in the etiology of these diseases. This inter-relationship offers potential avenues for novel diagnosis and treatment approaches.
Article
Immunology
Josephine Kemna, Evelyne Gout, Leon Daniau, Jessica Lao, Kristoffer Weissert, Sandra Ammann, Ralf Kuehn, Matthias Richter, Christine Molenda, Anje Sporbert, Dario Zocholl, Robert Klopfleisch, Hugues Lortat-Jacob, Peter Aichele, Thomas Kammertoens, Thomas Blankenstein
Summary: The study demonstrates that the extracellular matrix (ECM)-binding domain (EBD) of interferon-gamma (IFN gamma) is crucial for preventing high systemic levels of this cytokine and related immunopathology. Lack of EBD in IFN gamma significantly reduces ECM binding but retains the binding to IFN gamma receptor and bioactivity. Overexpression of EBD-deficient IFN gamma results in increased systemic levels, sickness behavior, weight loss, and toxicity.
Article
Multidisciplinary Sciences
Tanja Klein-Rodewald, Kateryna Micklich, Adrian Sanz-Moreno, Monica Tost, Julia Calzada-Wack, Thure Adler, Matthias Klaften, Sibylle Sabrautzki, Bernhard Aigner, Markus Kraiger, Valerie Gailus-Durner, Helmut Fuchs, Albert Gruender, Heike Pahl, Eckhard Wolf, Martin Hrabe de Angelis, Birgit Rathkolb
Summary: Gastro-intestinal stromal tumors and acute myeloid leukemia induced by activating stem cell factor receptor tyrosine kinase (KIT) mutations are highly malignant. The role of KIT mutations in breast cancer is unclear. Treatment success of KIT-induced cancers is still unsatisfactory due to resistance to therapy. Mouse models offer essential platforms for studies on molecular disease mechanisms. The C3H Kit(N824K/WT) mouse model allows for investigating the role of KIT mutations in breast cancer and identifying genetic and environmental modifiers of disease progression.
SCIENTIFIC REPORTS
(2022)
Article
Endocrinology & Metabolism
Gandhari Maity-Kumar, Lisa Staender, Meri DeAngelis, Sooyeon Lee, Anna Molenaar, Lore Becker, Lillian Garrett, Oana Amerie, Sabine M. Hoelter, Wolfgang Wurst, Helmut Fuchs, Annette Feuchtinger, Valerie Gailus-Durner, Cristina Garcia-Caceres, Ahmed E. Othman, Caroline Brockmann, Vanessa Schoeffling, Katja Beiser, Heiko Krude, Piotr A. Mroz, Susanna Hofmann, Jan Tuckermann, Richard D. DiMarchi, Martin Hrabe de Angelis, Matthias H. Tschoep, Paul T. Pfluger, Timo D. Mueller
Summary: In this study, researchers generated a new Mct8/Oatp1c1 double-knockout mouse model and demonstrated that this model could mimic key features of the Allan-Herndon-Dudley syndrome (AHDS). The findings suggest that the Mct8/Oatp1c1 dKO mice are a valuable preclinical model for evaluating drugs for the treatment of AHDS.
MOLECULAR METABOLISM
(2022)
Article
Biology
Andreas Franz, A. Ioana Weber, Marco Preussner, Nicole Dimos, Alexander Stumpf, Yanlong Ji, Laura Moreno-Velasquez, Anne Voigt, Frederic Schulz, Alexander Neumann, Benno Kuropka, Ralf Kuehn, Henning Urlaub, Dietmar Schmitz, Markus C. Wahl, Florian Heyd
Summary: This study investigates the regulation and functionality of species-specific alternative splicing, focusing on CAMK2B splice isoforms in primates. The researchers identify and characterize several primate-specific CAMK2B splice isoforms with altered kinetic properties and substrate specificity. They demonstrate that primate-specific CAMK2B alternative splicing is achieved through branch point weakening during evolution. By introducing a weaker branch point sequence into the mouse genome, they observe significant changes in Camk2b splicing and impairment of long-term potentiation, linking branch point-controlled CAMK2B alternative splicing to learning and memory.
LIFE SCIENCE ALLIANCE
(2022)
Article
Biochemistry & Molecular Biology
Patricia da Silva-Buttkus, Nadine Spielmann, Tanja Klein-Rodewald, Christine Schuett, Antonio Aguilar-Pimentel, Oana V. Amarie, Lore Becker, Julia Calzada-Wack, Lillian Garrett, Raffaele Gerlini, Markus Kraiger, Stefanie Leuchtenberger, Manuela A. Oestereicher, Birgit Rathkolb, Adrian Sanz-Moreno, Claudia Stoeger, Sabine M. Hoelter, Claudia Seisenberger, Susan Marschall, Helmut Fuchs, Valerie Gailus-Durner, Martin Hrabe de Angelis
Summary: Rare diseases pose challenges in medicine due to their diverse clinical manifestations and low prevalence. The lack of specific treatments for the majority of rare diseases highlights the need for research. Genome sequencing technology allows for the identification of potential disease-causing genes, but further confirmation is required. Mouse knockout models are crucial for studying the genetics of rare diseases and the German Mouse Clinic is a pioneer in this field. Collaboration between research institutions, clinicians, and patient groups is necessary to advance the understanding and treatment of rare diseases.
Correction
Immunology
Josephine Kemna, Evelyne Gout, Leon Daniau, Jessica Lao, Kristoffer Weissert, Sandra Ammann, Ralf Kuehn, Matthias Richter, Christine Molenda, Anje Sporbert, Dario Zocholl, Robert Klopfleisch, Hugues Lortat-Jacob, Peter Aichele, Thomas Kammertoens, Thomas Blankenstein
Article
Biology
Esther Stroo, Leen Janssen, Olga Sin, Wytse Hogewerf, Mirjam Koster, Liesbeth Harkema, Sameh A. Youssef, Natalie Beschorner, Anouk H. G. Wolters, Bjorn Bakker, Lore Becker, Lilian Garrett, Susan Marschall, Sabine M. Hoelter, Wolfgang Wurst, Helmut Fuchs, Valerie Gailus-Durner, Martin Hrabe de Angelis, Amanth Thathiah, Floris Foijer, Bart van de Sluis, Jan van Deursen, Matthias Jucker, Alain de Brun, Ellen A. A. Nollen
Summary: In age-related neurodegenerative diseases, disease-specific proteins form amyloid-like deposits. Depletion of SERF proteins can ameliorate this process. However, it is unknown whether SERF modifies amyloid pathology in mammalian brain.
LIFE SCIENCE ALLIANCE
(2023)
Article
Biochemistry & Molecular Biology
Howard T. Jacobs, Marten Szibor, Birgit Rathkolb, Patricia da Silva-Buttkus, Juan Antonio Aguilar-Pimentel, Oana V. Amarie, Lore Becker, Julia Calzada-Wack, Nathalia Dragano, Lillian Garrett, Raffaele Gerlini, Sabine M. Hoelter, Tanja Klein-Rodewald, Markus Kraiger, Stefanie Leuchtenberger, Susan Marschall, Manuela A. Oestereicher, Kristina Pfannes, Adrian Sanz-Moreno, Claudia Seisenberger, Nadine Spielmann, Claudia Stoeger, Wolfgang Wurst, Helmut Fuchs, Martin Hrabe de Angelis, Valerie Gailus-Durner
Summary: The alternative oxidase (AOX) can delay the onset and progression of respiratory-chain diseases, but it does not provide long-term benefit.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)