Article
Neurosciences
Nicole K. Morrill, Aurelie Joly-Amado, Qingyou Li, Sahana Prabhudeva, Edwin J. Weeber, Kevin R. Nash
Summary: This study found that the reduction in Reelin may be related to FXS, and enhancing the Reelin signaling successfully rescued cognitive deficits in FXS mice, providing a feasible therapeutic approach.
EXPERIMENTAL NEUROLOGY
(2022)
Review
Cell Biology
Rob Willemsen, R. Frank Kooy
Summary: Fragile X-related disorders are caused by expanded CGG repeats in the FMR1 gene and can manifest as either neurodegenerative or neurodevelopmental disorders. Mouse models have provided valuable insights into these disorders and their translational value for developing targeted therapies for intellectual disability and autism disorders.
DISEASE MODELS & MECHANISMS
(2023)
Article
Neurosciences
Xiaotong Wu, Yali Liu, Xiaomeng Wang, Lu Zheng, Libiao Pan, Hao Wang
Summary: This study reveals developmental impairment of thalamic relay synapses in individuals with fragile X syndrome, which may contribute to somatosensory over-reactivity.
NEUROSCIENCE BULLETIN
(2023)
Article
Psychiatry
Juan Pozo-Palacios, Arianne Llamos-Paneque, Christian Rivas, Emily Onofre, Andrea Lopez-Caceres, Jenniffer Villareal
Summary: Fragile X syndrome is a common genetic cause of intellectual disability, diagnosed through screening and detection of CGG repeats via PCR. A study in Ecuadorian males identified 22 potentially affected individuals with FXS through molecular analysis.
FRONTIERS IN PSYCHIATRY
(2021)
Article
Clinical Neurology
Carrie R. Jonak, Manbir S. Sandhu, Samantha A. Assad, Jacqueline A. Barbosa, Mahindra Makhija, Devin K. Binder
Summary: This study demonstrates the beneficial effects of the PDE10A inhibitor TAK-063 on normalizing EEG biomarkers in a mouse model of Fragile X syndrome, suggesting potential for further translational treatment development without noticeable side effects.
Article
Biochemistry & Molecular Biology
Gregory G. Vandenberg, Neal J. Dawson, Alison Head, Graham R. Scott, Angela L. Scott
Summary: Research suggests that mitochondrial dysfunction in astrocytes may contribute to oxidative stress in Fragile X Syndrome, leading to elevated levels of reactive oxygen species, potentially playing a role in the pathology of neurological disorders.
NEUROCHEMISTRY INTERNATIONAL
(2021)
Article
Neurosciences
Pan-Yue Deng, Oshri Avraham, Valeria Cavalli, Vitaly A. Klyachko
Summary: The study revealed pronounced hyperexcitability in peripheral sensory neurons in Fmr1 KO mice, primarily caused by dysfunction of HCN channels, with no significant changes observed in AP rising and falling time, peak potential, amplitude, or duration. Sensory dysfunction in the FXS mouse model may stem from contributions of both neuronal intrinsic and extrinsic mechanisms.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Article
Neurosciences
Francisco Altimiras, Jose Antonio Garcia, Ismael Palacios-Garcia, Michael J. Hurley, Robert Deacon, Bernardo Gonzalez, Patricia Cogram
Summary: The study found alterations in the gut microbiome of Fragile X syndrome (FXS) mouse model, including metabolic pathways associated with autism. This suggests a potential association of the gut microbiome with FXS, opening new possibilities for exploring reliable treatments and non-invasive biomarkers.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Neurosciences
Kathryn E. Reynolds, Chloe R. Wong, Angela L. Scott
Summary: Research indicates that there is dysregulation of purinergic signaling in astrocytes of Fragile X Syndrome patients, with increased intracellular calcium responses compared to wildtype. Additionally, levels of synaptogenic protein TSP-1, regulated by P2Y activation, were elevated in the FXS cortex, suggesting an increased potential for synaptic formation.
Article
Medicine, Research & Experimental
Karima Habbas, Oktay Cakil, Boglarka Zambo, Ricardos Tabet, Fabrice Riet, Doulaye Dembele, Jean-Louis Mandel, Michael Hocquemiller, Ralph Laufer, Francoise Piguet, Herve Moine
Summary: Fragile X syndrome (FXS) is a common form of familial intellectual disability caused by the lack of RNA-binding protein FMRP. This study demonstrates that DGKk, an mRNA target of FMRP and a regulator of lipid signaling, plays an important role in FXS pathogenesis, and the delivery of modified and FMRP-independent DGKk can correct abnormal lipid signaling and behavioral phenotypes in FXS mice.
EMBO MOLECULAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Byung Geun Ha, Jung-Yoon Heo, Yu-Jin Jang, Tae-Shin Park, Ju-Yeon Choi, Woo Young Jang, Sung-Jin Jeong
Summary: The study revealed that mitochondrial dysfunction in astrocytes of FXS model mice is associated with the pathogenesis of the disease, and can be monitored by depletion of mitochondrial components in EVs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Alexandra Lucas, Shani Poleg, Achim Klug, Elizabeth A. McCullagh
Summary: This study investigated defects in myelination in the auditory brainstem of FXS mice, revealing decreases in fiber diameter, myelin thickness, and axon diameter, as well as an increase in g-ratio. The findings suggest that changes in myelination characteristics may be related to an increase in both OL and OPCs in FXS mice.
FRONTIERS IN NEUROSCIENCE
(2021)
Review
Cell Biology
Azalea Lee, Jie Xu, Zhexing Wen, Peng Jin
Summary: Fragile X syndrome is the most common inherited cause of intellectual disability and autism spectrum disorder. Human induced pluripotent stem cells provide a unique means of studying FXS pathophysiology specific to humans.
Article
Biochemical Research Methods
Ruzena Filandrova, Pauline Douglas, Xiaoqin Zhan, Theodore B. Verhey, Sorana Morrissy, Raymond W. Turner, David C. Schriemer
Summary: The choice of appropriate methods for proteomics analysis is crucial for in-depth study of subtle changes in the proteome. In this study, seven different strategies were compared in a mouse model of Fragile X Syndrome. It was found that data-independent acquisition (DIA) and tandem mass tag (TMT)-based real-time search method (RTS) generated the most informative protein profiles. DIA and RTS methods uncovered known regulators of the syndrome and detected alterations in calcium signaling pathways. However, there were limitations in ratio compression and ion detection sensitivity for some of the methods used. The data are available via ProteomeXchange with the identifier PXD039885.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Clinical Neurology
Qi Ding, Xueting Wu, Xuan Li, Hongbing Wang
Summary: This study reveals the therapeutic effects of the FDA-approved drug vorinostat in a mouse model of FXS, suggesting its potential for clinical intervention in FXS.
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
(2022)
Editorial Material
Hematology
Elizabeth F. Stone, Scott T. Avecilla, David L. Wuest, Christine Lomas-Francis, Connie M. Westhoff, David L. Diuguid, Michel Sadelain, Farid Boulad, Patricia A. Shi
Article
Genetics & Heredity
Christopher Y. Park, Jian Zhou, Aaron K. Wong, Kathleen M. Chen, Chandra L. Theesfeld, Robert B. Darnell, Olga G. Troyanskaya
Summary: The research revealed the crucial role of RNA-binding proteins (RBPs) in psychiatric disorder risk, with the pathogenic contribution of noncoding variants impacting RBP target sites being a key factor. RBP dysregulation explains a significant amount of heritability not captured by large-scale studies and has a stronger impact.
Article
Cell Biology
Sean O'Connor, Elisabeth A. Murphy, Sarah K. Szwed, Matt Kanke, Francois Marchildon, Praveen Sethupathy, Robert B. Darnell, Paul Cohen
Summary: The study comprehensively analyzed the network of miRNA:mRNA interactions in white and brown fat using HITS-CLIP, revealing numerous unique AGO binding sites and an inverse correlation between depot-enriched miRNAs and their targets. Furthermore, experimental validation showed that miR-29 is a novel regulator of leptin expression, providing important insights into the unique identities of white and brown fat cells.
GENES & DEVELOPMENT
(2021)
Article
Medicine, General & Internal
Ezgi Hacisuleyman, Caryn Hale, Yuhki Saito, Nathalie E. Blachere, Marissa Bergh, Erin G. Conlon, Dennis J. Schaefer-Babajew, Justin DaSilva, Frauke Muecksch, Christian Gaebler, Richard Lifton, Michel C. Nussenzweig, Theodora Hatziioannou, Paul D. Bieniasz, Robert B. Darnell
Summary: Despite evidence of vaccine efficacy, two fully vaccinated individuals developed mild symptoms of Covid-19 and were infected with variants of SARS-CoV-2. Sequencing of the virus isolates revealed novel mutations, highlighting the potential risk of illness post-vaccination and subsequent infection with variant virus. Efforts to prevent, diagnose, and characterize variants in vaccinated individuals are crucial.
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Article
Medicine, Research & Experimental
Angelo D'Alessandro, Heather L. Howie, Ariel M. Hay, Karolina H. Dziewulska, Benjamin C. Brown, Matthew J. Wither, Matthew Karafin, Elizabeth F. Stone, Steven L. Spitalnik, Eldad A. Hod, Richard O. Francis, Xiaoyun Fu, Tiffany Thomas, James C. Zimring
Summary: G6PD deficiency is a common enzymopathy that may provide resistance to malaria, but also leads to hemolytic sequelae and is associated with various diseases. Generating a more accurate mouse model of G6PD deficiency has provided insights into altered metabolism and potential disease mechanisms.
Article
Cell Biology
Yuhki Saito, Ben R. Hawley, M. Rhyan Puno, Shreya N. Sarathy, Christopher D. Lima, Samie R. Jaffrey, Robert B. Darnell, Scott Keeney, Devanshi Jain
Summary: In this study, the researchers investigated how the N-6-methyladenosine (m(6)A) reader and RNA helicase YTHDC2 regulate gene expression during meiosis. They found that YTHDC2 can bind transcripts independent of m(6)A status and regulate gene expression through distinct mechanisms during multiple stages of meiosis. Mutation of the m(6)A-binding pocket of YTHDC2 had no effect on gametogenesis, suggesting that YTHDC2's function is m(6)A-independent. However, mutation in the ATPase motif of YTHDC2 blocked meiotic prophase I progression, causing sterility.
GENES & DEVELOPMENT
(2022)
Editorial Material
Hematology
Christine Lomas-Francis, Elizabeth F. Stone, Connie M. Westhoff, Patricia A. Shi
Article
Physiology
Christopher Y. Kim, Hannah Johnson, Sandy Peltier, Steven L. Spitalnik, Eldad A. Hod, Richard O. Francis, Krystalyn E. Hudson, Elizabeth F. Stone, Dominique E. Gordy, Xiaoyun Fu, James C. Zimring, Pascal Amireault, Paul W. Buehler, Robert B. Wilson, Angelo D'Alessandro, Mikhail S. Shchepinov, Tiffany Thomas
Summary: In this study, the effects of deuterated linoleic acid (DLA) on the storage quality of red blood cells (RBCs) were investigated. The results showed that DLA reduced lipid peroxidation, improved RBC deformability, filterability, and post-transfusion recovery. Particularly, the effects of DLA were more significant in mice with poor storage quality.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Cell Biology
Yoko Tajima, Keiichi Ito, Yuan Yuan, Mayu O. Frank, Yuhki Saito, Robert B. Darnell
Summary: We investigated the role of NOVA1 in postnatal motor inhibition by studying a patient with NOVA1 haploinsufficiency and a behavioral motor hyperactivity disorder. Through the generation of a conditional Nova1-null mouse, we found similarities between the phenotypes of these mice and the patient, indicating a function of Nova1 in the hypothalamus. Furthermore, NOVA1 loss in Gad2-positive neurons led to the dysregulation of downstream expression of Impact mRNA and other related factors, which are involved in translation and metabolism. These findings demonstrate the importance of NOVA1 in adult hypothalamic neurons and its role in human neurologic disease.
Article
Multidisciplinary Sciences
Matthew L. Mendoza, Lilyana D. Quiley, Thomas Dunhan, Lenora J. Volk
Summary: A growing body of literature suggests that KIBRA is involved in memory and neurodevelopmental disorders. This study uses knockout mice to show that deleting KIBRA in adult mice impairs long-term spatial memory and long-term potentiation (LTP), while deleting it in juvenile mice has minimal effects. The findings indicate that KIBRA plays a unique role in adult hippocampal function.
Article
Cell Biology
Camille Brewer, Tobias Lanz, Caryn R. Hale, Gregory D. Sepich-Poore, Cameron Martino, Austin D. Swafford, Thomas S. Carroll, Sarah Kongpachith, Lisa K. Blum, Serra E. Elliott, Nathalie E. Blachere, Salina Parveen, John Fak, Vicky Yao, Olga Troyanskaya, Mayu O. Frank, Michelle S. Bloom, Shaghayegh Jahanbani, Alejandro M. Gomez, Radhika Iyer, Nitya S. Ramadoss, Orr Sharpe, Sangeetha Chandrasekaran, Lindsay B. Kelmenson, Qian Wang, Heidi Wong, Holly L. Torres, Mark Wiesen, Dana T. Graves, Kevin D. Deane, V. Michael Holers, Rob Knight, Robert B. Darnell, William H. Robinson, Dana E. Orange
Summary: This study found that periodontal disease is more common in individuals with rheumatoid arthritis (RA) who have detectable anticitrullinated protein antibodies (ACPAs), suggesting a link between oral mucosal inflammation and RA pathogenesis. The researchers also discovered that RA patients with periodontal disease experienced repeated oral bacteremias associated with transcriptional signatures of specific monocyte subsets observed in inflamed RA synovia and blood during RA flares. The bacteremia was caused by citrullinated oral bacteria and resulted in activation of ACPA B cells, promoting affinity maturation and epitope spreading to citrullinated human antigens.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Cell Biology
Lilyana D. Quigley, Robert Pendry, Matthew L. Mendoza, Brad. E. Pfeiffer, Lenora J. Volk
Summary: Synaptic plasticity is hypothesized to contribute to the replay of salient experience during hippocampal SWR-based ensemble activity and facilitate memory consolidation. The synaptic protein KIBRA regulates plasticity and memory. Through studying WT and KIBRA cKO mice, it was found that KIBRA deletion disrupted experience-induced alterations in SWRs and hippocampal-cortical communication during SWRs.
Article
Multidisciplinary Sciences
Krithi Irmady, Caryn R. Hale, Rizwana Qadri, John Fak, Sitsandziwe Simelane, Thomas Carroll, Serge Przedborski, Robert B. Darnell
Summary: The ability to predict the outcomes of Parkinson's disease using blood samples would be clinically valuable. By analyzing the molecular profiles of postmortem brain tissue and peripheral blood, researchers identified molecular signatures associated with cognitive and motor complications, disease onset, and duration. These findings highlight the potential pathophysiologic and prognostic importance of molecular changes in the brain and peripheral blood of Parkinson's disease patients.
NATURE COMMUNICATIONS
(2023)
Letter
Medicine, General & Internal
Nathalie E. Blachere, Ezgi Hacisuleyman, Robert B. Darnell
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Article
Medicine, Research & Experimental
Max R. O'Donnell, Beatriz Grinsztejn, Matthew J. Cummings, Jessica E. Justman, Matthew R. Lamb, Christina M. Eckhardt, Neena M. Philip, Ying Kuen Cheung, Vinay Gupta, Esau Joao, Jose Henrique Pilotto, Maria Pia Diniz, Sandra Wagner Cardoso, Darryl Abrams, Kartik N. Rajagopalan, Sarah E. Borden, Allison Wolf, Leon Claude Sidi, Alexandre Vizzoni, Valdilea G. Veloso, Zachary C. Bitan, Dawn E. Scotto, Benjamin J. Meyer, Samuel D. Jacobson, Alex Kantor, Nischay Mishra, Lokendra Chauhan, Elizabeth F. Stone, Flavia Dei Zotti, Francesca La Carpia, Krystalyn E. Hudson, Stephen A. Ferrara, Joseph Schwartz, Brie A. Stotler, Wen-Hsuan W. Lin, Sandeep N. Wontakal, Beth Shaz, Thomas Briese, Eldad A. Hod, Steven L. Spitalnik, Andrew Eisenberger, Walter Lipkin
Summary: This study found that the use of convalescent plasma was not associated with significant improvement in the clinical status at day 28 for severe COVID-19 patients, but it was related to significantly improved survival rates.
JOURNAL OF CLINICAL INVESTIGATION
(2021)