Article
Multidisciplinary Sciences
Nathan P. Achilly, Wei Wang, Huda Y. Zoghbi
Summary: Research using a mouse model of Rett syndrome shows that intensive training before symptom onset can significantly improve specific motor and memory tasks, delaying the onset of symptoms. The study indicates that task-specific neurons activated during training develop more dendritic arbors and have better neurophysiological responses, enhancing their functionality and delaying symptom onset.
Article
Biochemistry & Molecular Biology
Yann Ehinger, Valerie Matagne, Valerie Cunin, Emilie Borloz, Michel Seve, Sandrine Bourgoin-Voillard, Ana Borges-Correia, Laurent Villard, Jean-Christophe Roux
Summary: Mutations in the X-linked MECP2 gene cause Rett syndrome, and a study identified the involvement of astroglial secreted proteins in the neuronal RTT phenotype in vitro. Lcn2 and Lgals3 were found to significantly increase dendritic arborization of neurons from Mecp2 KO mice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Nicolas Lebrun, Chloe Delepine, Mohamed Selloum, Hamid Meziane, Juliette Nectoux, Yann Herault, Thierry Bienvenu
Summary: Rett syndrome is a rare neurodevelopmental disorder, with more than 95% of cases linked to variants in the MECP2 gene. By modulating microtubule dynamics, the selective HDAC6 inhibitor tubastatin A can reverse exploratory behavior deficits associated with Rett syndrome.
Article
Neurosciences
Chiara Urbinati, Chiara Lanzillotta, Livia Cosentino, Daniela Valenti, Maria Cristina Quattrini, Livia Di Crescenzo, Francesca Prestia, Donatella Pietraforte, Marzia Perluigi, Fabio Di Domenico, Rosa Anna Vacca, Bianca De Filippis
Summary: Metformin treatment can selectively correct cognitive flexibility defects, improve mitochondrial function, and inhibit oxidative stress in female mice with Rett syndrome (RTT). However, it does not affect the general health and motor skills of RTT mice.
Article
Multidisciplinary Sciences
John R. Sinnamon, Michael E. Jacobson, John F. Yung, Jenna R. Fisk, Sophia Jeng, Shannon K. McWeeney, Lindsay K. Parmelee, Chi Ngai Chan, Siu-Pok Yee, Gail Mandel
Summary: This study provides evidence that a targeted RNA-editing approach can alleviate a hallmark symptom in a mouse model of Rett syndrome. Injection of a Mecp2-targeting virus effectively restores MeCP2 expression and function in the brainstem of mice, alleviating abnormal respiratory patterns and prolonging survival.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Catarina Miranda-Lourenco, Jessica Rosa, Nadia Rei, Rita F. Belo, Ana Luisa Lopes, Diogo Silva, Catia Vieira, Teresa Magalhaes-Cardoso, Ricardo Viais, Paulo Correia-de-Sa, Ana M. Sebastiao, Maria J. Diogenes
Summary: This study reveals significant changes in the BDNF and adenosine signaling pathways in a milder phenotype model of Rett Syndrome, suggesting that enhancing adenosinergic activity may be an effective therapeutic strategy for RTT patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Valentina Gigliucci, Jasper Teutsch, Marc Woodbury-Smith, Mirko Luoni, Marta Busnelli, Bice Chini, Abhishek Banerjee
Summary: The study found that Rett syndrome (RTT) is associated with deficits in KCC2 function and E/I balance. Treatment with recombinant human insulin-like growth factor-1 (rhIGF-1) and oxytocin (OXT) may restore KCC2 expression and normalize E/I balance. These findings provide new therapeutic strategies for RTT.
Article
Multidisciplinary Sciences
C. M. Cleary, S. James, B. J. Maher, D. K. Mulkey
Summary: Disordered breathing is a hallmark of Pitt-Hopkins syndrome (PTHS), and targeting central Nav1.8 channels may improve behavioral abnormalities associated with PTHS.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Ipek Akol, Annalisa Izzo, Fabian Gather, Stefanie Strack, Stefanie Heidrich, Darren O. Hailin, Alejandro Villarreal, Christine Hacker, Tudor Rauleac, Chiara Bella, Andre Fischer, Thomas Manke, Tanja Vogel
Summary: Forkhead box G1 (FOXG1) plays important roles in neuronal differentiation and maintaining excitatory/inhibitory balance in the network. In this study, the authors investigated how FOXG1 impacts neuronal maturation at the chromatin level in the mouse hippocampus. They found that FOXG1 regulates transcription, binds to enhancer regions, and alters the epigenetic landscape. FOXG1 and NEUROD1 act cooperatively to control neuronal maturation, and the chromatin alterations affect synaptogenesis and axonogenesis. This study provides insights into the multimodality of FOXG1 functions and suggests epigenetic drugs as potential therapeutic options for neuronal dysfunction.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Neurosciences
Parker K. Stevenson, Devin M. Casenhiser, Billy Y. B. Lau, Keerthi Krishnan
Summary: The study reveals atypical behavioral patterns in a female mouse model for Rett syndrome during pup retrieval, such as abnormal pup approach and grooming interactions. Individual animals across different genotypes and strains show dynamic changes in goal-related movements during the study.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Giuseppe Pepe, Salvatore Fioriniello, Federico Marracino, Luca Capocci, Vittorio Maglione, Maurizio D'Esposito, Alba Di Pardo, Floriana Della Ragione
Summary: Rett syndrome is a severe neurodevelopmental disorder caused by pathogenetic variants in the MECP2 gene. This study found that Rett syndrome patients have impaired brain vascular homeostasis and blood-brain barrier breakdown, which may contribute to the cognitive impairment. The study provides evidence of impaired blood-brain barrier integrity in Rett syndrome and offers new perspectives for novel therapeutic strategies.
Article
Immunology
Huiping Li, Meixin Hu, Zhuxi Huang, Yi Wang, Ying Xu, Jingxin Deng, Ming Zhu, Weijun Feng, Xiu Xu
Summary: Mecp2-deficient mice show increased numbers of B cells and CD8(+) T cells in the meninges, as well as enhanced immune-related processes. This study reveals the significant role of meningeal immunity in Rett syndrome.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Neurosciences
Valerie Matagne, Emilie Borloz, Yann Ehinger, Lydia Saidi, Laurent Villard, Jean-Christophe Roux
Summary: Rett syndrome is a severe neurodevelopmental disorder caused by mutations in the MECP2 gene, and gene therapy has shown some efficacy in improving symptoms but further research is needed. Severe side effects were observed when using high doses of the vector, including liver damage and apoptosis.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Cell Biology
Yingyao Shao, Yehezkel Sztainberg, Qi Wang, Sameer S. Bajikar, Alexander J. Trostle, Ying-Wooi Wan, Paymaan Jafar-Nejad, Frank Rigo, Zhandong Liu, Jianrong Tang, Huda Y. Zoghbi
Summary: Research has shown that using ASO therapy can effectively reduce the amount of MeCP2 protein in MDS mouse models and reverse the disease features. By generating an MDS mouse model with two human MECP2 alleles and administering MECP2-ASO through intracerebroventricular injection, it was found to efficiently down-regulate MeCP2 expression throughout the brain and improve disease features without toxicity.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Neurosciences
Sheryl Anne D. Vermudez, Aditi Buch, Kelly Weiss, Rocco M. Gogliotti, Colleen M. Niswender
Summary: Rett syndrome and MECP2 Duplication syndrome have opposite molecular origins, but share some clinical and preclinical phenotypes. Modulating mGlu2 and mGlu3 receptors may be a potential treatment option for both disorders.
Review
Neurosciences
William H. Barnett, Ana P. Abdala, Julian F. R. Paton, Ilya A. Rybak, Daniel B. Zoccal, Yaroslav I. Molkov
EXPERIMENTAL NEUROLOGY
(2017)
Article
Neurosciences
Cristina Paula do Nascimento, Gabriella Xavier Maretto, Graziany Leite Moreira Marques, Luciana Mesquita Passamani, Ana Paula Abdala, Luiz Carlos Schenberg, Vanessa Beijamini, Karla Nivea Sampaio
NEUROTOXICITY RESEARCH
(2017)
Article
Neurosciences
William H. Barnett, Sarah E. M. Jenkin, William K. Milsom, Julian F. R. Paton, Ana P. Abdala, Yaroslav I. Molkov, Daniel B. Zoccal
JOURNAL OF NEUROPHYSIOLOGY
(2018)
Article
Neurosciences
P. S. Hosford, V. Mosienko, K. Kishi, G. Jurisic, K. Seuwen, B. Kinzel, M. G. Ludwig, J. A. Wells, I. N. Christie, L. Koolen, A. P. Abdala, B. H. Liu, A. V. Gourine, A. G. Teschemacher, S. Kasparov
Article
Genetics & Heredity
Angus John Clarke, Ana Paula Abdala Sheikh
ORPHANET JOURNAL OF RARE DISEASES
(2018)
Article
Neurosciences
Samuel Wittman, Ana Paula Abdala, Jonathan E. Rubin
JOURNAL OF PHYSIOLOGY-LONDON
(2019)
Article
Cardiac & Cardiovascular Systems
Hongwei Cheng, Chunyun Du, Yihong Zhang, Andrew F. James, Christopher E. Dempsey, Ana P. Abdala, Jules C. Hancox
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2019)
Article
Physiology
Pedro Lourenco Katayama, Ana Paula Abdala, Ian Charles, Wioletta Pijacka, Helio Cesar Salgado, Joel Gever, Anthony P. Ford, Julian F. R. Paton
RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY
(2020)
Editorial Material
Clinical Neurology
Anna Maria Lavezzi, Ana Paula Abdala, William P. Fifer
FRONTIERS IN NEUROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Hongwei Cheng, Ian Charles, Andrew F. James, Ana P. Abdala, Jules C. Hancox
Summary: This study investigated the ECG and ventricular AP characteristics in the Mecp2(Null/Y) male murine RTT model and found QT and QRS prolongation, as well as increased AP duration and instability. It also revealed an increase in I-Na,I-Late in the RTT myocytes. The inhibitor GS-6615 showed potential as a treatment for QT prolongation in RTT. These findings are important for understanding and treating RTT.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Neurosciences
Julian F. R. Paton, Benedito H. Machado, Davi J. A. Moraes, Daniel B. Zoccal, Ana P. Abdala, Jeffrey C. Smith, Vagner R. Antunes, David Murphy, Mathias Dutschmann, Rishi R. Dhingra, Robin McAllen, Anthony E. Pickering, Richard J. A. Wilson, Trevor A. Day, Nicole O. Barioni, Andrew M. Allen, Clement Menuet, Joseph Donnelly, Igor Felippe, Walter M. St-John
Summary: This review article discusses the progress and potential future applications of the working heart-brainstem preparation (WHBP) in cardiovascular, neuroendocrine, autonomic and respiratory research. The WHBP is a novel in situ experimental model that provides unprecedented access and stability for studying physiological mechanisms. It has revealed new insights into various mechanisms related to respiratory rhythms, sympathetic activity, coupling between respiration and the heart, control mechanisms in the hypothalamus and spinal cord, and chemoreceptor mechanisms. These findings have been validated in vivo and have translated to humans. The article also discusses potential future applications of the WHBP, such as two-photon imaging and pharmacogenetic tools, for improving our understanding and treatment of cardiorespiratory diseases.
JOURNAL OF PHYSIOLOGY-LONDON
(2022)
Article
Physiology
Hongwei Cheng, Ian Charles, Andrew F. James, Ana P. Abdala, Jules C. Hancox
Summary: This study investigates the ECG and ventricular action potential characteristics of Mecp2(Null/+) female mice. The results show prolonged QT intervals and delayed repolarization in Mecp2(Null/+) mice, and suggest the potential of GS-6615 as an intervention for QT prolongation in RTT.
PHYSIOLOGICAL REPORTS
(2022)
Article
Cardiac & Cardiovascular Systems
Zoe H. Adams, Hazel C. Blythe, Nisha Charkoudian, Timothy B. Curry, Michael J. Joyner, Adrian H. Kendrick, Angus K. Nightingale, Ana P. Abdala Sheikh, Emma C. Hart
Summary: Respiratory modulation of sympathetic nerve activity is reduced in postmenopausal females, which is associated with higher resting blood pressure.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2023)
Article
Neurosciences
S. R. John, W. H. Barnett, A. P. L. Abdala, D. B. Zoccal, J. E. Rubin, Y. I. Molkov
Summary: The Kolliker-Fuse nucleus (KF) plays a crucial role in both normal breathing and respiratory abnormalities, such as those seen in Rett syndrome. However, little is known about the dynamics of KF neurons and their synaptic connections. In this study, computational models were used to investigate the activity of KF and its interactions with other components of the respiratory neural circuitry. Two models were developed to simulate normal breathing and breathing abnormalities, and their properties were found to be consistent with experimental observations. These findings provide insights into the dynamics and local network interactions of KF, and offer predictions for future experimental testing.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Pedro Lourenco Katayama, Ian Charles, Wioletta Pijacka, Ana Paula Abdala, Helio Cesar Salgado, Anthony P. Ford, Julian F. R. Paton