Article
Multidisciplinary Sciences
Sunil Krishna, Bokun Cheng, Deep R. Sharma, Sunita Yadav, Erin S. Stempinski, Sahil Mamtani, Elisa Shah, Anjali Deo, Trishna Acherjee, Teena Thomas, Xusheng Zhang, Jinghang Zhang, Dumitru A. Iacobas, Praveen Ballabh
Summary: Activation of PPAR-γ enhances myelination and neurological function in preterm rabbits with IVH, but does not reduce hydrocephalus. Treatment with PPAR-γ agonist may enhance myelination and neurological recovery in premature infants with IVH.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Ana Palma, Juan Carlos Chara, Alejandro Montilla, Amaia Otxoa-de-Amezaga, Francisca Ruiz-Jaen, Anna M. Planas, Carlos Matute, Alberto Perez-Samartin, Maria Domercq
Summary: Abnormalities in myelination are associated with behavioral and cognitive dysfunction in neurodevelopmental psychiatric disorders. Clemastine, a drug that promotes myelination, has complex effects on myelin development during the developmental process. The study found that clemastine treatment increased oligodendrocyte differentiation but decreased conduction velocity and myelin thickness in the corpus callosum. Additionally, the population of microglia cells and insulin growth factor-1 levels decreased in clemastine-treated mice.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Megan Chesnut, Helene Paschoud, Cendrine Repond, Lena Smirnova, Thomas Hartung, Marie-Gabrielle Zurich, Helena T. Hogberg, David Pamies
Summary: Myelin is crucial for the central nervous system, and differences between human and rodent oligodendrocytes make animals inadequate for modeling related diseases. Developing human in vitro models has been challenging but 3D cell cultures derived from iPSCs can now partially reproduce the myelination process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Megan Chesnut, Thomas Hartung, Helena Hogberg, David Pamies
Summary: Neurodevelopment is highly sensitive to toxic insults, and there is a lack of evaluation on the potential developmental neurotoxicity (DNT) of most commonly used chemicals. Using human cell-based in vitro systems for testing DNT chemicals can aid in prioritizing them based on their effects on neurodevelopment, but there is a limited number of in vitro models for myelination, which is a fundamental process in neurodevelopment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Carmela Serpe, Lucia Monaco, Michela Relucenti, Ludovica Iovino, Pietro Familiari, Ferdinando Scavizzi, Marcello Raspa, Giuseppe Familiari, Laura Civiero, Igea D'Agnano, Cristina Limatola, Myriam Catalano
Summary: The study demonstrates that microglia-derived sEVs affect cancer cell metabolism by carrying miR-124, reducing the release of certain chemicals by glioma cells, and increasing the expression of Glu transporter Glt-1 on astrocytes. This in turn leads to significantly reduced tumor mass and increased survival of glioma-bearing mice, depending on miR-124.
Article
Biochemistry & Molecular Biology
Jane Melissa Lim, Rumi Lee, Yeonsil Kim, In Young Lee, Eunju Kim, Eui-Ju Choi
Summary: This study demonstrates that excessive activation of NMDA receptor leads to excitotoxic neuronal death by increasing calcium influx. The cleavage and activation of MST1 by calpain 1, mediated by NMDA, promotes excitotoxicity in mouse cortical neurons.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Review
Cell Biology
Weida Shen, Jelena Bogdanovic Pristov, Paola Nobili, Ljiljana Nikolic
Summary: Epilepsy is a neurological disorder with approximately 30% of patients being resistant to current medications. Recent research suggests that the role of glial cells in epilepsy should be considered, as their supportive roles and interaction with neurons are disrupted in epileptic brains. Dysfunction of glial cells, such as astroglial potassium channels, water channels, gap junctions, glutamate transporters, purinergic signaling, synaptogenesis, microglial inflammatory cytokines, microglia-astrocyte interactions, and oligodendroglial potassium channels, may contribute to abnormal neuronal activity and can be potential targets for new anti-epileptic drugs.
NEURAL REGENERATION RESEARCH
(2023)
Article
Clinical Neurology
Kathryn Pellerin, Stephen J. Rubino, Jeremy C. Burns, Benjamin A. Smith, Christie-Ann Mccarl, Jing Zhu, Luke Jandreski, Patrick Cullen, Thomas M. Carlile, Angela Li, Jorge Vera Rebollar, Jennifer Sybulski, Taylor L. Reynolds, Baohong Zhang, Rebecca Basile, Hao Tang, Chelsea Parker Harp, Alex Pellerin, John Silbereis, Nathalie Franchimont, Ellen Cahir-McFarland, Richard M. Ransohoff, Thomas O. Cameron, Michael Mingueneau
Summary: The study reveals the pathophysiological significance of autoantibody-induced Fc receptor signaling in the central nervous system, depending on central Fc receptor engagement in microglia proliferation. The activation of Fc receptors and BTK signaling in microglia provides a novel in vivo tool to further explore the roles of microglia-specific Fc receptor and BTK-driven responses in CNS homeostasis and disease.
Article
Cell Biology
Mariarosaria Cammarota, Francesca Boscia
Summary: The understanding of myelin processing under neuroinflammation is crucial for studying inflammation resolution and neuroprotection. A three-dimensional experimental model using hippocampal explants provides valuable insights into the spatial-temporal contribution of glial scarring to myelin uptake and processing.
Review
Biochemistry & Molecular Biology
Yan Zhang, John-Man-Tak Chu, Gordon-Tin-Chun Wong
Summary: This article reviews how glutamate handling and glutamatergic function are affected by neuroinflammation and their contribution to cognitive impairment. The authors summarize the current data regarding glutamate in neurotransmission, including its receptors and regulation. They also examine the impact of inflammation on glutamate handling and neurotransmission, focusing on changes in glial cells and the effect of cytokines. Finally, they discuss the implications of these changes for perioperative neuroinflammation and perioperative neurocognitive disorders.
Article
Oncology
Yitong Wang, Xiangyu Ge, Shu Yu, Qiong Cheng
Summary: ABPPk can alleviate neurotoxicity of LPS-activated microglia by inhibiting the expression of NLRP3 and cleaved caspase 1, reducing the release of inflammatory factors, and decreasing the toxic effects of LPS-activated microglia on neurons.
ANNALS OF TRANSLATIONAL MEDICINE
(2021)
Review
Cell Biology
Danica Nheu, Olivia Ellen, Sining Ye, Ezgi Ozturk, Maurice Pagnin, Stephen Kertadjaja, Paschalis Theotokis, Nikolaos Grigoriadis, Catriona McLean, Steven Petratos
Summary: Current therapeutics for chronic phases of multiple sclerosis (MS) have limitations in reversing neural damage caused by inflammation and demyelination. Our research suggests that blocking the activation of microglia can be a potential therapeutic strategy to limit neuroinflammation and neurodegeneration in MS. This review explores the role and polarization of microglia in MS pathology, as well as the potential of targeting Nogo-A/NgR cellular mechanisms for neurorepair in MS and other demyelination diseases.
Article
Neurosciences
Sheri L. Peterson, Yiqing Li, Christina J. Sun, Kimberly A. Wong, Kylie S. Leung, Silmara de Lima, Nicholas J. Hanovice, Kenya Yuki, Beth Stevens, Larry Benowitz
Summary: This study reveals the essential role of local optic nerve complement and myeloid phagocytic signaling in central nervous system axon regeneration, emphasizing the importance of the axonal compartment in CNS repair. Additionally, the study highlights the beneficial neuroimmune role of complement and microglia/monocytes in facilitating axon regrowth through myelin phagocytosis within the optic nerve, shedding light on the innate immune response for CNS repair.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Environmental Sciences
Dongying Yan, Liang Gao, Jing Lang, Xianhui Gao, Honglin Ma
Summary: Excessive exposure to manganese can lead to neurological diseases characterized by behavioral and motor impairments. Microglia-mediated neuroinflammation plays a key role in the pathogenesis of neurodegenerative diseases. SIRT1, PGC-1 alpha, NF-kappa B, and STAT3 are important factors in the regulation of neuroinflammatory responses and microglial polarization in mice exposed to manganese.
ENVIRONMENTAL TOXICOLOGY
(2021)
Article
Immunology
Ya-Nan Zhang, Jing-Kai Fan, Li Gu, Hui-Min Yang, Shu-Qin Zhan, Hong Zhang
Summary: The research demonstrated that mGluR5 inhibits alpha-synuclein-induced microglia inflammation to protect against neurotoxicity, while alpha-synuclein promotes the degradation of mGluR5 through lysosomal pathway to accelerate neuroinflammation. This novel mechanism may serve as a potential therapeutic target for Parkinson's disease.
JOURNAL OF NEUROINFLAMMATION
(2021)
Article
Cell Biology
Manasi Jiwrajka, Alexandra Phillips, Matt Butler, Miriam Rossi, Jennifer M. Pocock
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
(2016)
Article
Biochemical Research Methods
Claire L. Russell, Amanda Heslegrave, Vikram Mitra, Henrik Zetterberg, Jennifer M. Pocock, Malcolm A. Ward, Ian Pike
RAPID COMMUNICATIONS IN MASS SPECTROMETRY
(2017)
Article
Neurosciences
Jennifer M. Pocock, Thomas M. Piers
NATURE REVIEWS NEUROSCIENCE
(2018)
Article
Cell Biology
Pablo Garcia-Reitboeck, Alexandra Phillips, Thomas M. Piers, Claudio Villegas-Llerena, Matt Butler, Anna Mallach, Celia Rodrigues, Charles E. Arber, Amanda Heslegrave, Henrik Zetterberg, Harald Neumann, Stephen Neame, Henry Houlden, John Hardy, Jennifer M. Pocock
Article
Neurosciences
Thomas M. Piers, Emma East, Claudio Villegas-Llerena, Ioanna G. Sevastou, Mar Matarin, John Hardy, Jennifer M. Pocock
FRONTIERS IN CELLULAR NEUROSCIENCE
(2018)
Correction
Neurosciences
Claudie Hooper, Ricardo Sainz-Fuertes, Steven Lynham, Abdul Hye, Richard Killick, Alice Warley, Cecilia Bolondi, Jennifer Pocock, Simon Lovestone
Article
Biochemistry & Molecular Biology
Thomas M. Piers, Katharina Cosker, Anna Mallach, Gabriel Thomas Johnson, Rita Guerreiro, John Hardy, Jennifer M. Pocock
Article
Immunology
Grace C. O'Regan, Sahar H. Farag, Caroline S. Casey, Alison Wood-Kaczmar, Jennifer M. Pocock, Sarah J. Tabrizi, Ralph Andre
Summary: The study demonstrated that human Huntington's disease pluripotent stem cell-derived microglia are hyper-reactive due to their autonomous expression of mutant HTT, providing a cellular mechanism for the potential contribution of neuroinflammation to the pathogenesis of Huntington's disease.
JOURNAL OF NEUROINFLAMMATION
(2021)
Article
Biochemistry & Molecular Biology
Iqra Nazish, Charles Arber, Thomas M. Piers, Thomas T. Warner, John A. Hardy, Patrick A. Lewis, Jennifer M. Pocock, Rina Bandopadhyay
Summary: Our study revealed that LRRK2-dependent Rab10 phosphorylation is modulated by LPS stimulation, and cytokine release may be influenced by the status of LRRK2. This provides new insights into the immune response function of LRRK2.
NEUROCHEMISTRY INTERNATIONAL
(2021)
Article
Multidisciplinary Sciences
Katharina Cosker, Anna Mallach, Janhavi Limaye, Thomas M. Piers, James Staddon, Stephen J. Neame, John Hardy, Jennifer M. Pocock
Summary: The study revealed that microglia carrying the TREM2 R47H variant have impaired response to cell damage signals, potentially contributing to the progression of late onset Alzheimer's disease.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Anna Mallach, Johan Gobom, Charles Arber, Thomas M. Piers, John Hardy, Selina Wray, Henrik Zetterberg, Jennifer Pocock
Summary: Microglial exosomes play a crucial role in communication and transmission of neurodegenerative signals. Variations in exosomal proteome, influenced by the R47H(het) TREM2 variant, may contribute to the increased risk of Alzheimer's disease. Exosomes from R47H(het) iPS-Mg were found to have weaker effects on promoting neuronal processes compared to those from the common TREM2 variant iPS-Mg.
Article
Neurosciences
Jingzhang Wei, Charles Arber, Selina Wray, John Hardy, Thomas M. M. Piers, Jennifer M. M. Pocock
Summary: One type of early life stress, prenatal exposure to glucocorticoids (GCs), increases the risk of psychiatric and neurodevelopmental disorders in later life. Microglial cells are being increasingly recognized for their importance in these disorders. However, research on GCs exposure during microglial development is limited, especially in human studies. In this study, an in vitro model of early life stress was established by pre-exposing human iPS-microglia to GCs during primitive hematopoiesis, and the effects on microglial phenotype were examined. The findings suggest that prolonged GCs exposure during primitive hematopoiesis leads to changes in the matured iPS-microglia, potentially contributing to ELS-associated disorders.
Article
Neurosciences
Alma S. Popescu, Claire A. Butler, David H. Allendorf, Thomas M. Piers, Anna Mallach, Julian Roewe, Peter Reinhardt, Alessandro Cinti, Loredana Redaelli, Christophe Boudesco, Laurent Pradier, Jennifer M. Pocock, Peter Thornton, Guy C. Brown
Summary: R47H TREM2 may increase the risk of AD by enhancing the phagocytosis of synapses and neurons through greater activation by phosphatidylserine. WT TREM2 may decrease the microglial phagocytosis of synapses and neurons via cystatin F.
Article
Clinical Neurology
Anna Mallach, Johan Gobom, Henrik Zetterberg, John Hardy, Thomas M. Piers, Selina Wray, Jennifer M. Pocock
Summary: Variants in the triggering receptor expressed on myeloid cells 2 gene are associated with an increased risk of dementia, with the R47H(het) variant linked specifically to late-onset Alzheimer's disease. Differences were observed in the quantity and composition of exosomes secreted by common variant controls and R47H(het) variants, with the latter showing weaker protective effects on stressed neurons. These findings suggest potential targets for therapeutic interventions in Alzheimer's disease.
BRAIN COMMUNICATIONS
(2021)
Article
Clinical Neurology
Charles Arber, Claudio Villegas-Llerena, Jamie Toombs, Jennifer M. Pocock, Natalie S. Ryan, Nick C. Fox, Henrik Zetterberg, John Hardy, Selina Wray
BRAIN COMMUNICATIONS
(2019)
Article
Biochemistry & Molecular Biology
Pei-Yang Gao, Ya-Nan Ou, Yi-Ming Huang, Zhi-Bo Wang, Yan Fu, Ya-Hui Ma, Qiong-Yao Li, Li-Yun Ma, Rui-Ping Cui, Yin-Chu Mi, Lan Tan, Jin-Tai Yu
Summary: Liver function may play a role in the progression of Alzheimer's disease. The study found that as AD progressed, certain liver function markers increased while others decreased. The relationship between liver function and CSF AD biomarkers indicates a potential mediation effect on cognition.
JOURNAL OF NEUROCHEMISTRY
(2024)