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Folia Neuropathologica 2020Lipopolysaccharide (LPS) is a potent immunogen when administered locally and/or systemically. The peripheral immunization with LPS could contribute to the progression... (Review)
Review
Lipopolysaccharide (LPS) is a potent immunogen when administered locally and/or systemically. The peripheral immunization with LPS could contribute to the progression of neurological diseases because a strong link between neuroinflammation and dopaminergic degeneration has been found. The switch between the survival and neuronal death in substantia nigra could be related to M1 (neurotoxic) and M2 (neuroprotective) microglia phenotypes. In this review, we present the current findings about microglia roles, biomarkers, and natural or synthetic immune modulators determined in the LPS-based murine model.
Topics: Animals; Cell Differentiation; Disease Models, Animal; Humans; Inflammation; Lipopolysaccharides; Microglia
PubMed: 32729290
DOI: 10.5114/fn.2020.96755 -
Brain Pathology (Zurich, Switzerland) Nov 2020
Topics: Central Nervous System; Humans; Microglia; Myeloid Cells
PubMed: 33064365
DOI: 10.1111/bpa.12907 -
Current Opinion in Genetics &... Dec 2020Microglia are instrumental to the development, function, homeostasis and pathologies of the central nervous system. These brain-resident macrophages arise early in... (Review)
Review
Microglia are instrumental to the development, function, homeostasis and pathologies of the central nervous system. These brain-resident macrophages arise early in embryogenesis and seed the developing brain, where they differentiate in response to cues provided by their neural niche. Throughout life, microglia regulate the neural tissue through a variety of cellular functions influenced by intrinsic and extrinsic factors. Despite their importance, we are only starting to uncover how microglia colonize the brain, adopt distinct functional states during development and the long-term impact of early alteration of their functions. This review highlights the latest knowledge on the ontogeny of microglia, their developmental trajectory and emerging roles. Characterizing these processes will be critical for our understanding of both brain physiology and pathologies.
Topics: Animals; Brain; Homeostasis; Humans; Macrophages; Microglia; Neurodevelopmental Disorders; Neurogenesis
PubMed: 32823206
DOI: 10.1016/j.gde.2020.06.013 -
Aging Cell Feb 2021Metformin, a drug widely used for treating diabetes, can prolong the lifespan in several species. Metformin also has the promise to slow down age-related cognitive...
Metformin, a drug widely used for treating diabetes, can prolong the lifespan in several species. Metformin also has the promise to slow down age-related cognitive impairment. However, metformin's therapeutic use as an anti-aging drug is yet to be accepted because of conflicting animal and human studies results. We examined the effects of metformin treatment in late middle age on cognitive function in old age. Eighteen-month-old male C57BL6/J mice received metformin or no treatment for 10 weeks. A series of behavioral tests revealed improved cognitive function in animals that received metformin. Such findings were evident from a better ability for pattern separation, object location, and recognition memory function. Quantification of microglia revealed that metformin treatment reduced the incidence of pathological microglial clusters with alternative activation of microglia into an M2 phenotype, displaying highly ramified processes in the hippocampus. Metformin treatment also seemed to reduce astrocyte hypertrophy. Additional analysis demonstrated that metformin treatment in late middle age increased adenosine monophosphate-activated protein kinase activation, reduced proinflammatory cytokine levels, and the mammalian target of rapamycin signaling, and enhanced autophagy in the hippocampus. However, metformin treatment did not alter neurogenesis or synapses in the hippocampus, implying that improved cognitive function with metformin did not involve enhanced neurogenesis or neosynaptogenesis. The results provide new evidence that metformin treatment commencing in late middle age has promise for improving cognitive function in old age. Modulation of microglia, proinflammatory cytokines, and autophagy appear to be the mechanisms by which metformin facilitated functional benefits in the aged brain.
Topics: Aging; Animals; Autophagy; Cognition; Hippocampus; Male; Metformin; Mice; Mice, Inbred C57BL; Microglia
PubMed: 33443781
DOI: 10.1111/acel.13277 -
Neuroscience Bulletin Mar 2023As prominent immune cells in the central nervous system, microglia constantly monitor the environment and provide neuronal protection, which are important functions for... (Review)
Review
As prominent immune cells in the central nervous system, microglia constantly monitor the environment and provide neuronal protection, which are important functions for maintaining brain homeostasis. In the diseased brain, microglia are crucial mediators of neuroinflammation that regulates a broad spectrum of cellular responses. In this review, we summarize current knowledge on the multifunctional contributions of microglia to homeostasis and their involvement in neurodegeneration. We further provide a comprehensive overview of therapeutic interventions targeting microglia in neurodegenerative diseases. Notably, we propose microglial depletion and subsequent repopulation as promising replacement therapy. Although microglial replacement therapy is still in its infancy, it will likely be a trend in the development of treatments for neurodegenerative diseases due to its versatility and selectivity.
Topics: Humans; Microglia; Central Nervous System; Neurodegenerative Diseases; Brain; Homeostasis
PubMed: 36593381
DOI: 10.1007/s12264-022-01013-6 -
Neurochemical Research Sep 2022Ischemic tolerance is a phenomenon in which resistance to subsequent invasive ischemia is acquired by a preceding noninvasive ischemic application, and is observed in... (Review)
Review
Ischemic tolerance is a phenomenon in which resistance to subsequent invasive ischemia is acquired by a preceding noninvasive ischemic application, and is observed in many organs, including the brain, the organ most vulnerable to ischemic insult. To date, much research has been conducted on cerebral ischemic tolerance as a cell-autonomous action of neurons. In this article, we review the essential roles of microglia and astrocytes in the acquisition of ischemic tolerance through neuron-non-autonomous mechanisms, where the two types of glial cells function in a concerted manner to induce ischemic tolerance.
Topics: Astrocytes; Brain Ischemia; Humans; Ischemia; Ischemic Preconditioning; Microglia
PubMed: 35920970
DOI: 10.1007/s11064-022-03704-y -
Frontiers in Immunology 2022Microglia are mononuclear phagocytes of mesodermal origin that migrate to the central nervous system (CNS) during the early stages of embryonic development. After... (Review)
Review
Microglia are mononuclear phagocytes of mesodermal origin that migrate to the central nervous system (CNS) during the early stages of embryonic development. After colonizing the CNS, they proliferate and remain able to self-renew throughout life, maintaining the number of microglia around 5-12% of the cells in the CNS parenchyma. They are considered to play key roles in development, homeostasis and innate immunity of the CNS. Microglia are exceptionally diverse in their morphological characteristics, actively modifying the shape of their processes and soma in response to different stimuli. This broad morphological spectrum of microglia responses is considered to be closely correlated to their diverse range of functions in health and disease. However, the morphophysiological attributes of microglia, and the structural and functional features of microglia-neuron interactions, remain largely unknown. Here, we assess the current knowledge of the diverse microglial morphologies, with a focus on the correlation between microglial shape and function. We also outline some of the current challenges, opportunities, and future directions that will help us to tackle unanswered questions about microglia, and to continue unravelling the mysteries of microglia, in all its shapes.
Topics: Microglia; Central Nervous System; Neurons; Homeostasis
PubMed: 36341385
DOI: 10.3389/fimmu.2022.997786 -
Journal of Neuroendocrinology Mar 2020Microglia have been known for decades as key immune cells that shape the central nervous system (CNS) during development and respond to brain pathogens and injury in... (Review)
Review
Microglia have been known for decades as key immune cells that shape the central nervous system (CNS) during development and respond to brain pathogens and injury in adult life. Recent findings now suggest that these cells also play a highly complex role in several other functions of the CNS. In this review, we provide a brief overview of the established microglial functions in development and disease. We also discuss emerging research suggesting that microglia are important for both cognitive function and the regulation of food intake. With respect to cognitive function, current data suggest microglia are not indispensable for neurogenesis, synaptogenesis or cognition in the healthy young adult, although they crucially modulate and support these functions. In doing so, they are likely important in supporting the balance between apoptosis and survival of newborn neurones and in orchestrating appropriate synaptic remodelling in response to a learning stimulus. We also explore the possibility of a role for microglia in feeding and satiety. Microglia have been implicated in both appetite suppression with sickness and obesity and in promoting feeding under some conditions and we discuss these findings here, highlighting the contribution of these cells to healthy brain function.
Topics: Animals; Brain; Cognition; Humans; Microglia; Neurons; Satiation
PubMed: 32097992
DOI: 10.1111/jne.12838 -
CNS Neuroscience & Therapeutics Mar 2020A large number of families worldwide suffer from the physical and mental burden posed by stroke. An increasing number of studies aimed at the prevention and treatment of... (Review)
Review
A large number of families worldwide suffer from the physical and mental burden posed by stroke. An increasing number of studies aimed at the prevention and treatment of stroke have been conducted. Specifically, manipulating the immune response to stroke is under intense investigation. Microglia are the principal immune cells in the brain and are the first line of defense against the pathophysiology induced by stroke. Increasing evidence has suggested that microglia play diverse roles that depend on dynamic interactions with neurons, astrocytes, and other neighboring cells both in the normal brain and under pathological conditions, including stroke. Moreover, there are dynamic alterations in microglial functions with respect to aging and sex differences in the human brain, which offer a deep understanding of the conditions of stroke patients of different ages and sex. Hence, we review the dynamic microglial reactions caused by aging, sex, and crosstalk with neighboring cells both in normal conditions and after stroke and relevant potential interventions.
Topics: Aging; Animals; Brain; Humans; Microglia; Neurons; Sex Characteristics; Stroke
PubMed: 32064759
DOI: 10.1111/cns.13291 -
Acta Neuropathologica Feb 2022Microglia, the resident myeloid cells in the central nervous system (CNS) play critical roles in shaping the brain during development, responding to invading pathogens,... (Review)
Review
Microglia, the resident myeloid cells in the central nervous system (CNS) play critical roles in shaping the brain during development, responding to invading pathogens, and clearing tissue debris or aberrant protein aggregations during ageing and neurodegeneration. The original concept that like macrophages, microglia are either damaging (pro-inflammatory) or regenerative (anti-inflammatory) has been updated to a kaleidoscope view of microglia phenotypes reflecting their wide-ranging roles in maintaining homeostasis in the CNS and, their contribution to CNS diseases, as well as aiding repair. The use of new technologies including single cell/nucleus RNA sequencing has led to the identification of many novel microglia states, allowing for a better understanding of their complexity and distinguishing regional variations in the CNS. This has also revealed differences between species and diseases, and between microglia and other myeloid cells in the CNS. However, most of the data on microglia heterogeneity have been generated on cells isolated from the cortex or whole brain, whereas white matter changes and differences between white and grey matter have been relatively understudied. Considering the importance of microglia in regulating white matter health, we provide a brief update on the current knowledge of microglia heterogeneity in the white matter, how microglia are important for the development of the CNS, and how microglial ageing affects CNS white matter homeostasis. We discuss how microglia are intricately linked to the classical white matter diseases such as multiple sclerosis and genetic white matter diseases, and their putative roles in neurodegenerative diseases in which white matter is also affected. Understanding the wide variety of microglial functions in the white matter may provide the basis for microglial targeted therapies for CNS diseases.
Topics: Animals; Central Nervous System Diseases; Humans; Microglia; White Matter
PubMed: 34878590
DOI: 10.1007/s00401-021-02389-x