Article
Biochemistry & Molecular Biology
Marije J. D. Huitema, Eva M. M. Strijbis, Antonio Luchicchi, John G. J. M. Bol, Jason R. Plemel, Jeroen J. G. Geurts, Geert J. Schenk
Summary: Multiple sclerosis is a demyelinating and neurodegenerative disease of the central nervous system. This study introduced and validated a novel standardized method for more precise myelin quantification in progressive MS brains. The method showed excellent inter-rater agreement and reliability in quantifying myelin content in human post-mortem samples.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Clinical Neurology
Vanja Tepavcevi, Catherine Lubetzki
Summary: The failure of remyelination in multiple sclerosis (MS) is often characterized by low oligodendrocyte progenitor cell density. Stimulating this process may be crucial for achieving myelin regeneration.
Article
Neurosciences
Mari Paz Serrano-Regal, Laura Bayon-Cordero, Juan Carlos Chara Ventura, Blanca Ochoa-Bueno, Vanja Tepavcevic, Carlos Matute, Maria Victoria Sanchez-Gomez
Summary: The GABA(B)R agonist baclofen has the potential to enhance oligodendrocyte progenitor cell differentiation and remyelination, suggesting it as a potential therapeutic strategy to stimulate remyelination in patients with multiple sclerosis (MS).
Review
Neurosciences
Kelley C. C. Atkinson, Marvellous Osunde, Seema K. K. Tiwari-Woodruff
Summary: Multiple sclerosis (MS) is a degenerative disorder of the central nervous system (CNS) with mitochondrial energy production failure. Mitochondrial morphology changes and impaired transport contribute to neurodegeneration and disability in MS. Current methodologies for studying mitochondria in MS only provide a partial understanding, and cell-specific studies in animal models are needed for a comprehensive understanding.
FRONTIERS IN NEUROSCIENCE
(2023)
Review
Neurosciences
Zahra Rashidbenam, Ezgi Ozturk, Maurice Pagnin, Paschalis Theotokis, Nikolaos Grigoriadis, Steven Petratos
Summary: Multiple sclerosis (MS) is a neurodegenerative disease that is caused by chronic inflammation, leading to neural cell loss and neuroaxonal dystrophy. Immune-mediated mechanisms can cause myelin debris accumulation, which hinders neurorepair and plasticity. This review focuses on the molecular and cellular mechanisms of neurodegeneration in MS and proposes therapeutic approaches to counteract myelin-associated inhibitory factors (MAIFs), such as Nogo-A, to promote neurorepair.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Review
Neurosciences
Thomas J. Scheinok, Miguel D'Haeseleer, Guy Nagels, Dimitri De Bundel, Jeroen Van Schependom
Summary: Oligodendrocytes are responsible for myelinating CNS axons for rapid electrical transmission. In multiple sclerosis (MS), demyelination occurs due to an inflammatory cascade. Therapies promoting remyelination, such as modulation of neuronal activity through non-invasive brain stimulation (NIBS), have shown promising results. However, the mechanisms behind NIBS and its effect on oligodendrogenesis and myelination are not fully understood.
PROGRESS IN NEUROBIOLOGY
(2023)
Article
Neurosciences
James J. M. Cooper, Jessie J. Polanco, Darpan Saraswat, Jennifer J. Peirick, Anna Seidl, Yi Li, Dan Ma, Fraser J. Sim
Summary: The failure of remyelination in the human CNS is a major contributor to axonal injury and disease progression in multiple sclerosis (MS). Murine models show a high density of oligodendrocyte progenitor cells (OPCs) in areas of demyelination, suggesting that efficient OPC repopulation is necessary for successful remyelination. However, in this study, we found that OPC repopulation was low in large lesions and almost absent in small lesions in adult rabbits, suggesting that both lesion volume and species-specific mechanisms play a role in regulating OPC proliferation and remyelination.
Review
Neurosciences
Karina Maciak, Angela Dziedzic, Joanna Saluk
Summary: Remyelination depends on the repair of damaged myelin sheaths, involving microglia cells, oligodendrocyte precursor cells (OPCs), and mature oligodendrocytes. Short, noncoding RNA molecules, microRNAs (miRNAs), are believed to play a crucial role in the remyelination process by regulating gene expression. Various delivery systems, including extracellular vesicles, hold promise as an efficient and non-invasive way for providing miRNAs to stimulate remyelination.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Ilias Kalafatakis, Domna Karagogeos
Summary: This review summarizes the regulation of myelination by oligodendrocytes under physiological and pathological conditions, as well as the role of microglia in myelin generation, regeneration, and repair. The beneficial and detrimental roles of microglia in remyelination are discussed, along with the cellular and molecular components involved. Recent findings related to preclinical models using human stem cells for studying microglia in human pathologies and the impact of the microbiome on glial cell functions are also presented.
Article
Multidisciplinary Sciences
Eduardo Caverzasi, Nico Papinutto, Christian Cordano, Gina Kirkish, Tristan J. Gundel, Alyssa Zhu, Amit Vijay Akula, W. John Boscardin, Heiko Neeb, Roland G. Henry, Jonah R. Chan, Ari J. Green
Summary: This study demonstrates that clemastine can induce myelin repair in patients with MS, and proposes myelin water fraction within the normal-appearing white matter of fibers as an imaging biomarker for assessing myelin restoration.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Clinical Neurology
Rafael Canani Sommer, Junichi Hata, Carolina de Medeiros Rimkus, Bruna Klein da Costa, Jin Nakahara, Douglas Kazutoshi Sato
Summary: Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system that impairs the activation of oligodendrocyte progenitor cells, which are crucial for remyelination. Conventional MRI sequences have limited ability to differentiate unmyelinated and remyelinated lesions, while advanced MRI sequences provide more accurate evaluation of remyelination.
MULTIPLE SCLEROSIS AND RELATED DISORDERS
(2022)
Article
Neuroimaging
Shannon Kolind, Shawna Abel, Carolyn Taylor, Roger Tam, Cornelia Laule, David K. B. Li, Hideki Garren, Laura Gaetano, Corrado Bernasconi, David Clayton, Irene Vavasour, Anthony Traboulsee
Summary: Ocrelizumab appears to protect against demyelination in multiple sclerosis patients and may provide a more favorable environment for remyelination.
NEUROIMAGE-CLINICAL
(2022)
Article
Endocrinology & Metabolism
Maria Santa Rocca, Giovanni Minervini, Cinzia Vinanzi, Alberto Bottacin, Federica Lia, Carlo Foresta, Maria Pennuto, Alberto Ferlin
Summary: This study evaluated the frequency and type of androgen receptor (AR) gene variants in a large cohort of infertile males. The study found that patients with AR gene variants had lower sperm count, higher testosterone concentration, and higher androgen sensitivity index compared to patients without variants. Two novel potentially pathogenic AR variants were identified. Based on these findings, AR sequencing is suggested as a routine genetic test in cases of idiopathic oligozoospermia with high testosterone levels.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Article
Pharmacology & Pharmacy
Yue Jia, Dandan Zhang, Haoran Li, Shaolei Luo, Yuhuan Xiao, Li Han, Fuchun Zhou, Chuanyue Wang, Lei Feng, Gang Wang, Peng Wu, Chunjie Xiao, Haijing Yu, Jing Du, Hongkun Bao
Summary: GAA significantly enhances remyelination and rescues motor deficiency in two animal models of MS by modulating the neuroimmune system and enhancing anti-inflammatory and regeneration markers, while inhibiting inflammatory markers. The novel therapeutic agent GAA acts through an FXR receptor-dependent mechanism to rescue MS neuroimmune imbalance and promote remyelination. Clinical investigation is needed to further explore the therapeutic effect of GAA in improving remyelination and rescuing motor function in MS patients.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Simone Patergnani, Massimo Bonora, Selene Ingusci, Maurizio Previati, Saverio Marchi, Silvia Zucchini, Mariasole Perrone, Mariusz R. Wieckowski, Massimiliano Castellazzi, Maura Pugliatti, Carlotta Giorgi, Michele Simonato, Paolo Pinton
Summary: The study found that autophagy and mitophagy are increased in MS patients, with inhibitors of autophagy improving myelination and behavioral signs in experimental models of the disease, suggesting a causal role of autophagy in MS and potential therapeutic benefits of autophagy inhibitors like haloperidol and clozapine.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Editorial Material
Medicine, Research & Experimental
Delnia Ahmadpour, Sakina Mhaouty-Kodja, Valerie Grange-Messent
M S-MEDECINE SCIENCES
(2022)
Article
Environmental Sciences
Amelie Crepet, Paule Vasseur, Julien Jean, Pierre-Marie Badot, Fabrice Nesslany, Jean-Paul Vernoux, Cyril Feidt, Sakina Mhaouty-Kodja
Summary: This study proposes a methodological approach to assess the chemical risk of contaminant mixtures in food and the environment, even in the absence of specific data on the effects and modes of action of the mixture components. By applying this method to contaminants in breast milk, the study identified the main contributors to the risk of neurodevelopmental and thyroid effects for infants, highlighting the importance of considering mixtures and identifying risk drivers in environmental contamination risk regulation.
ENVIRONMENTAL HEALTH PERSPECTIVES
(2022)
Article
Environmental Sciences
Pascal Vaudin, Corinne Auge, Nathalie Just, Sakina Mhaouty-Kodja, Stephane Mortaud, Delphine Pillon
Summary: Pharmaceutical drugs have become consumer products and environmental pollutants due to their volume of production and consumption. This article discusses the potential effects of antibiotics, antidepressants, and non-steroidal anti-inflammatory drugs on neurodevelopment, along with experimental studies and brain imaging in assessing their adverse effects.
ENVIRONMENTAL RESEARCH
(2022)
Article
Environmental Sciences
Claire Beausoleil, Brigitte Le Magueresse-Battistoni, Catherine Viguie, Sylvie Babajko, Marie-Chantal Canivenc-Lavier, Nicolas Chevalier, Claude Emond, Rene Habert, Nicole Picard-Hagen, Sakina Mhaouty-Kodja
Summary: The study compared the similarities between BPS and BPA, revealing potential adverse effects of BPS on human health at lower doses. Inconsistencies in toxicity were found between academic and regulatory studies for BPS, suggesting the need to establish human reference values for exposure to BPS based on academic findings.
ENVIRONMENTAL RESEARCH
(2022)
Article
Environmental Sciences
Delnia Ahmadpour, Sakina Mhaouty-Kodja, Valerie Grange-Messent
Summary: This study found that exposure of adult male mice to low doses of di(2-ethylhexyl)phthalate (DEHP) can lead to loss of blood-brain barrier (BBB) integrity and damage in the medial preoptic area (mPOA) involved in male sexual behavior. The exposure to DEHP resulted in reduced androgen receptor (AR) levels and decreased components of the basement membrane and cell-matrix interaction, leading to neurodegeneration. The findings suggest that environmental exposure to endocrine disruptors like phthalates can disrupt glio-neurovascular coupling and alter sexual behavior.
ENVIRONMENTAL RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Petra Bloms-Funke, Michael Schumacher, Song Liu, Diya Su, Jing Li, Philippe Liere, Rainer Rupprecht, Caroline Nothdurfter, Gregor Bahrenberg, Thomas Christoph, Christopher Habermann, Christa Kneip, Wolfgang Schroeder, Thomas M. Tzschentke, Derek Saunders
Summary: CNP, a chronic neuropathic pain, cannot be effectively prevented or reversed by opioids, necessitating the development of non-opioid options. GRT-X, a novel drug, acts on multiple mechanisms to enhance neuroprotection and neuroregeneration, showing potential as a treatment for CNP.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Nathalie Printemps, Brigitte Le Magueresse-Battistoni, Sakina Mhaouty-Kodja, Catherine Viguie, Cecile Michel
Summary: This review provides an overview of the assessment of the endocrine disrupting properties of carbon disulfide and highlights the challenges in differentiating a specific endocrine disruption from an indirect endocrine effect resulting from systemic toxicity. The study concludes that the adverse effects of carbon disulfide may be due to systemic toxicity rather than endocrine-mediated toxicity. It also raises questions about the capability of current toxicological techniques to address complex issues with certainty.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Nolwenn Adam, Sakina Mhaouty-Kodja
Summary: Phthalates have been shown to have reproductive toxic effects in male rodents, and can also impact the female rodent brain. Research indicates that exposure to phthalates may affect behaviors in female rodents, highlighting the need for further investigation to assess the potential risks to human health.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Rainer Rupprecht, Christian H. Wetzel, Mario Dorostkar, Jochen Herms, Nathalie L. Albert, Jens Schwarzbach, Michael Schumacher, Inga D. Neumann
Summary: Efficient treatment of stress-related disorders remains challenging. Neurosteroids show rapid therapeutic effects, but long-term use is limited by tolerance and side effects. Promoting endogenous neurosteroidogenesis via TSPO could provide a new treatment option.
MOLECULAR PSYCHIATRY
(2022)
Article
Biology
Anne-Charlotte Trouillet, Suzanne Ducroq, Lydie Naule, Daphne Capela, Caroline Parmentier, Sally Radovick, Helene Hardin-Pouzet, Sakina Mhaouty-Kodja
Summary: The neural deletion of estrogen receptor, ER α, primarily affects sexual behavior in female mice, while only having a moderate effect in male mice. This contrasts with previous studies that found ER α to be essential for reproductive behavior in both sexes.
COMMUNICATIONS BIOLOGY
(2022)
Article
Environmental Sciences
Ai Thu Bui, Sophia Houari, Sophia Loiodice, Dominique Bazin, Jeremy Sadoine, Nicolas Roubier, Elsa Vennat, Thu Thuy Tran, Ariane Berdal, Jean-Marc Ricort, Sakina Mhaouty-Kodja, Sylvie Babajko
Summary: This study analyzed the effects of exposure to low doses of DEHP on mouse teeth. The results showed that DEHP can directly affect dental cells, leading to impaired enamel development. Additionally, the study found delayed effects of DEHP on enamel hardness and mineralization. These findings are important for understanding the impact of environmental toxicant exposure and providing early markers.
ENVIRONMENTAL HEALTH PERSPECTIVES
(2022)
Article
Environmental Sciences
Nolwenn Adam, Marie-Amelie Lachayze, Caroline Parmentier, Helene Hardin-Pouzet, Sakina Mhaouty-Kodja
Summary: This study examined the effects of exposure to DEHP, an organic pollutant, on maternal behavior in mice. The findings suggest that exposure to DEHP can alter maternal behavior, possibly through neuroendocrine pathways involving oxytocin and estrogen.
ENVIRONMENTAL POLLUTION
(2022)
Article
Multidisciplinary Sciences
Amina Zahaf, Abdelmoumen Kassoussi, Tom Hutteau-Hamel, Amine Mellouk, Corentine Marie, Lida Zoupi, Foteini Tsouki, Claudia Mattern, Pierre Bobe, Michael Schumacher, Anna Williams, Carlos Parras, Elisabeth Traiffort
Summary: The neuroprotective, anti-inflammatory, and remyelinating properties of androgens have been well documented in demyelinated male mice and men with multiple sclerosis. However, the effects of androgens mediated by the androgen receptor (AR) in females with low androgen levels have been poorly studied. This study reveals a significant expression of AR in microglial cells in demyelinated lesions of female mice and women with multiple sclerosis, while AR expression is almost undetectable in lesions from male animals and men with multiple sclerosis. Additionally, androgens and estrogens act synergistically in female mice, with androgens driving microglial cell response towards regeneration. Transcriptomic comparisons of demyelinated mouse spinal cords show that androgens up-regulate genes related to neuronal function and myelin production, but down-regulate immune system genes in females and lipid catabolism genes in males. These findings highlight the importance of considering male-female differences in therapeutic approaches for demyelinating diseases as androgens are necessary for proper myelin regeneration in females.
NATURE COMMUNICATIONS
(2023)
Article
Environmental Sciences
Bin Bin Wang, Chao Guo, Sheng Qiao Sun, Xing Nan Zhang, Zhen Li, Wei Jie Li, De Zhi Li, Michael Schumacher, Song Liu
Summary: This study compared the effect of different peripheral nerve injury models on nerve regeneration through animal experiments. It was found that the regeneration speed was faster in the crush injury model, while it was slower in the transection injury model. This provides some reference for the selection of clinical research models.
BIOMEDICAL AND ENVIRONMENTAL SCIENCES
(2023)
Review
Toxicology
G. Jean Harry, Sandra McBride, Shannah K. Witchey, Sakina Mhaouty-Kodja, Alain Trembleau, Matthew Bridge, Anna Bencsik
Summary: Neurobehavioral phenotyping and assessment has experienced a resurgence in recent decades, resulting in a robust database on rodent performance and its associations with human disorders and therapeutic interventions. However, the use of behavior to assess environmental neurotoxicity is still questioned. Applying new paradigms and understanding the biological basis of behavior can help minimize variability and maximize information in neurobehavioral testing.
FRONTIERS IN TOXICOLOGY
(2022)