Microglia are macrophages residing in the central nervous system, where they perform immune surveillance, synaptic remodeling, neurogenesis, and monitor signals arising from brain injuries or potential pathogens.Commonly, rodent models are used for studying microglia because of the available transgenic mouse lines in which specific genetic manipulations are successfully accomplished. However, human and rodents microglia showed significant differences, which are reflected in different morphological and functional properties. These differences are in genetic and transcriptomic, but also in the expression of signaling molecules and age-associated changes.Several strategies are available to study human microglia, as using surgical brain resections from epileptic and tumoral tissues and from post mortem brain samples. In addition, the generation of human-induced pluripotent stem cells (hPSCs) and the possibility to differentiate them in microglia-like cells provide unique opportunities to compare microglia functions between rodents' and human brain.The use of human ex vivo and in vitro brain models allows the study of human microglia, mimicking in vivo conditions. This will be useful for a better understanding of the real live behavior and functions of microglia in the human brain. This chapter aims to highlight significant similarities and differences between human and rodent microglia in order to re-evaluate mouse models of different human brain disorders, proposing the use of in vitro and ex vivo human brain models.Studies on living human microglia in the brain may help to define divergences from animal models and to improve clinical interventions to treat brain pathologies, using alternatives targets.
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http://dx.doi.org/10.1007/978-3-031-55529-9_31 | DOI Listing |
FEBS Open Bio
January 2025
Sunny BioDiscovery Inc., Santa Paula, CA, USA.
Dimethyl fumarate (DMF) is an anti-inflammatory and immunoregulatory medication used to treat multiple sclerosis (MS) and psoriasis. Its skin sensitization property precludes its topical use, which is unfortunate for the treatment of psoriasis. Isosorbide di-(methyl fumarate) (IDMF), a novel derivative of DMF, was synthesized to circumvent this adverse reaction and unlock the potential of topical delivery, which could be useful for treating psoriasis in the subpopulation of psoriatic MS patients, as well as in the general population.
View Article and Find Full Text PDFNat Neurosci
January 2025
School of Integrative and Global Majors, University of Tsukuba, Tsukuba, Japan.
Microglia-resident immune cells in the central nervous system-undergo morphological and functional changes in response to signals from the local environment and mature into various homeostatic states. However, niche signals underlying microglial differentiation and maturation remain unknown. Here, we show that neuronal micronuclei (MN) transfer to microglia, which is followed by changing microglial characteristics during the postnatal period.
View Article and Find Full Text PDFCommun Biol
January 2025
Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Histological chorioamnionitis (HCA) is a form of maternal immune activation (MIA) linked to an increased risk of neurodevelopmental disorders in offspring. Our previous study identified neurodevelopmental impairments in an MIA mouse model mimicking HCA. Thus, this study investigated the role of CD11c microglia, key contributors to myelination through IGF-1 production, in this pathology.
View Article and Find Full Text PDFFree Neuropathol
January 2024
Department of Pathology, Nash Family Department of Neuroscience, Department of Artificial Intelligence & Human Health, Neuropathology Brain Bank & Research CoRE, Ronald M. Loeb Center for Alzheimer's Disease, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
This review highlights a collection of both diverse and highly impactful studies published in the previous year selected by the author from the neurodegenerative neuropathology literature. As with previous reviews in this series, the focus is, to the best of my ability, to highlight human tissue-based experimentation most relevant to experimental and clinical neuropathologists. A concerted effort was made to balance the selected studies across neurodegenerative disease categories, approaches, and methodologies to capture the breadth of the research landscape.
View Article and Find Full Text PDFSubcell Biochem
January 2025
Faculty of Medicine and Faculty of Life Sciences, Institute of Biomedical Sciences (ICB), Universidad Andres Bello, Santiago, Chile.
Healthy brain functioning requires a continuous fine-tuning of gene expression, involving changes in the epigenetic landscape and 3D chromatin organization. Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD) are three multifactorial neurodegenerative diseases (NDDs) that are partially explained by genetics (gene mutations and genetic risk factors) and influenced by non-genetic factors (i.e.
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