scholarly journals The multicellular interplay of microglia in health and disease: lessons from leukodystrophy

2021 ◽  
Vol 14 (8) ◽  
Author(s):  
Woutje M. Berdowski ◽  
Leslie E. Sanderson ◽  
Tjakko J. van Ham
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
White Matter ◽  
Genetic Disorders ◽  
Brain Dysfunction ◽  
Brain Diseases ◽  
Human Patient ◽  
The Central Nervous System ◽  
The Impact

ABSTRACT Microglia are highly dynamic cells crucial for developing and maintaining lifelong brain function and health through their many interactions with essentially all cellular components of the central nervous system. The frequent connection of microglia to leukodystrophies, genetic disorders of the white matter, has highlighted their involvement in the maintenance of white matter integrity. However, the mechanisms that underlie their putative roles in these processes remain largely uncharacterized. Microglia have also been gaining attention as possible therapeutic targets for many neurological conditions, increasing the demand to understand their broad spectrum of functions and the impact of their dysregulation. In this Review, we compare the pathological features of two groups of genetic leukodystrophies: those in which microglial dysfunction holds a central role, termed ‘microgliopathies’, and those in which lysosomal or peroxisomal defects are considered to be the primary driver. The latter are suspected to have notable microglia involvement, as some affected individuals benefit from microglia-replenishing therapy. Based on overlapping pathology, we discuss multiple ways through which aberrant microglia could lead to white matter defects and brain dysfunction. We propose that the study of leukodystrophies, and their extensively multicellular pathology, will benefit from complementing analyses of human patient material with the examination of cellular dynamics in vivo using animal models, such as zebrafish. Together, this will yield important insight into the cell biological mechanisms of microglial impact in the central nervous system, particularly in the development and maintenance of myelin, that will facilitate the development of new, and refinement of existing, therapeutic options for a range of brain diseases.

Advances in Imaging Multiple Sclerosis

2017 ◽  
Vol 37 (05) ◽  
pp. 538-545 ◽  
Author(s):  
Eduardo Caverzasi ◽  
Christian Cordano ◽  
Stephen Hauser ◽  
Roland Henry ◽  
Antje Bischof
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Emission Tomography ◽  
Resonance Imaging ◽  
Ms Imaging ◽  
Positron Emission ◽  
The Central Nervous System ◽  
The Impact

Neuroimaging has emerged as a powerful technology that has enabled visualization of the impact of multiple sclerosis (MS) on the central nervous system in vivo with unprecedented precision. It has played a crucial role in disentangling the chronology of inflammation and neurodegeneration, developing and understanding mechanisms of novel therapeutics, and diagnosing and monitoring the disease in the clinical setting. However, challenges pertaining to the limited resolution, lack of specificity, inherent technological biases, and processing of increasingly big datasets have hindered comprehensive insights into the pathology underlying disability.Here, we review the advances in neuroimaging for MS that have moved the field forward in recent years by addressing the above-mentioned issues, thereby enhancing our knowledge of this yet enigmatic disease. We discuss complementary imaging technologies, including magnetic resonance imaging, positron emission tomography, and optical coherence tomography, the most recent tool in the MS imaging armamentarium that holds promise to act as a surrogate of pathological changes in the central nervous system in a more easily accessible way.

scholarly journals Microglia-Induced Maladaptive Plasticity Can Be Modulated by NeuropeptidesIn Vivo

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Stefano Morara ◽  
Anna Maria Colangelo ◽  
Luciano Provini
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neural Circuit ◽  
Critical Role ◽  
Adult Life ◽  
Experimental Models ◽  
Brain Diseases ◽  
Maladaptive Plasticity ◽  
The Central Nervous System

Microglia-induced maladaptive plasticity is being recognized as a major cause of deleterious self-sustaining pathological processes that occur in neurodegenerative and neuroinflammatory diseases. Microglia, the primary homeostatic guardian of the central nervous system, exert critical functions both during development, in neural circuit reshaping, and during adult life, in the brain physiological and pathological surveillance. This delicate critical role can be disrupted by neural, but also peripheral, noxious stimuli that can prime microglia to become overreactive to a second noxious stimulus or worsen underlying pathological processes. Among regulators of microglia, neuropeptides can play a major role. Their receptors are widely expressed in microglial cells and neuropeptide challenge can potently influence microglial activityin vitro. More relevantly, this regulator activity has been assessed alsoin vivo, in experimental models of brain diseases. Neuropeptide action in the central nervous system has been associated with beneficial effects in neurodegenerative and neuroinflammatory pathological experimental models. This review describes some of the mechanisms of the microglia maladaptive plasticityin vivoand how neuropeptide activity can represent a useful therapeutical target in a variety of human brain pathologies.

scholarly journals Toxicity of metallic nanoparticles in the central nervous system

2019 ◽  
Vol 8 (1) ◽  
pp. 175-200 ◽  
Author(s):  
Krzysztof Sawicki ◽  
Magdalena Czajka ◽  
Magdalena Matysiak-Kucharek ◽  
Berta Fal ◽  
Bartłomiej Drop ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Metallic Nanoparticles ◽  
Current Knowledge ◽  
Negative Effects ◽  
Scientific Publications ◽  
The Central Nervous System ◽  
The Impact

Abstract Metallic nanoparticles due to their small size and unique physico-chemical characteristics have found excellent applications in various branches of industry and medicine. Therefore, for many years a growing interest has been observed among the scientific community in the improvement of our understanding of the impact of nanoparticles on the living organisms, especially on humans. Considering the delicate structure of the central nervous systemit is one of the organs most vulnerable to the adverse effects of metallic nanoparticles. For that reason, it is important to identify the modes of exposure and understand the mechanisms of the effect of nanoparticles on neuronal tissue. In this review, an attempt is undertaken to present current knowledge about metallic nanoparticles neurotoxicity based on the selected scientific publications. The route of entry of nanoparticles is described, as well as their distribution, penetration through the cell membrane and the blood-brain barrier. In addition, a study on the neurotoxicity in vitro and in vivo is presented, as well as some of the mechanisms that may be responsible for the negative effects of metallic nanoparticles on the central nervous system. Graphical abstract: This review summarizes the current knowledge on the toxicity of metallic NPs in the brain and central nervous system of the higher vertebrates.

scholarly journals Disrupting the leukemia niche in the central nervous system attenuates leukemia chemoresistance

2019 ◽  
Author(s):  
Leslie M. Jonart ◽  
Maryam Ebadi ◽  
Patrick Basile ◽  
Kimberly Johnson ◽  
Jessica Makori ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Lymphoblastic Leukemia ◽  
Leukemia Cells ◽  
Adhesion Assay ◽  
Hematopoietic Stem ◽  
The Central Nervous System ◽  
The Impact

AbstractProtection from acute lymphoblastic leukemia (ALL) relapse in the central nervous system (CNS) is crucial to survival and quality of life for ALL patients. Current CNS-directed therapies cause significant toxicities and are only partially effective. Moreover, the impact of the CNS microenvironment on leukemia biology is poorly understood. Herein, we showed that leukemia cells associated with the meninges of xenotransplanted mice, or co-cultured with meningeal cells, exhibit enhanced chemoresistance due to effects on both apoptosis balance and quiescence. From a mechanistic standpoint, we identified that leukemia chemoresistance is primarily mediated by direct leukemia-meningeal cell interactions and overcome by detaching the leukemia cells from the meninges. Next, we used a co-culture adhesion assay to identify drugs that disrupted leukemia-meningeal adhesion. In addition to identifying several drugs that inhibit canonical cell adhesion targets we found that Me6TREN, a novel hematopoietic stem cell (HSC) mobilizing compound, also disrupts leukemia-meningeal adhesion in vitro and in vivo. Finally, Me6TREN enhanced the efficacy of cytarabine in treating CNS leukemia in xenotransplanted mice. This work demonstrates that the meninges exert a critical influence on leukemia chemoresistance, elucidates mechanisms of CNS relapse beyond the well-described role of the blood-brain barrier, and identifies novel therapeutic approaches for overcoming chemoresistance.

scholarly journals Plant Species of Sub-Family Valerianaceae—A Review on Its Effect on the Central Nervous System

Plants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 846
Author(s):  
Gitishree Das ◽  
Han-Seung Shin ◽  
Rosa Tundis ◽  
Sandra Gonçalves ◽  
Ourlad Alzeus G. Tantengco ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Plant Species ◽  
Current Knowledge ◽  
Biological Properties ◽  
In Vivo Studies ◽  
Food Species ◽  
The Central Nervous System ◽  
Preclinical And Clinical Studies

Valerianaceae, the sub-family of Caprifoliaceae, contains more than 300 species of annual and perennial herbs, worldwide distributed. Several species are used for their biological properties while some are used as food. Species from the genus Valeriana have been used for their antispasmodic, relaxing, and sedative properties, which have been mainly attributed to the presence of valepotriates, borneol derivatives, and isovalerenic acid. Among this genus, the most common and employed species is Valerianaofficinalis. Although valerian has been traditionally used as a mild sedative, research results are still controversial regarding the role of the different active compounds, the herbal preparations, and the dosage used. The present review is designed to summarize and critically describe the current knowledge on the different plant species belonging to Valerianaceae, their phytochemicals, their uses in the treatment of different diseases with particular emphasis on the effects on the central nervous system. The available information on this sub-family was collected from scientific databases up until year 2020. The following electronic databases were used: PubMed, Scopus, Sci Finder, Web of Science, Science Direct, NCBI, and Google Scholar. The search terms used for this review included Valerianaceae, Valeriana, Centranthus, Fedia, Patrinia, Nardostachys, Plectritis, and Valerianella, phytochemical composition, in vivo studies, Central Nervous System, neuroprotective, antidepressant, antinociceptive, anxiolytic, anxiety, preclinical and clinical studies.

A radiotracer method for the measurement of central nervous system catecholamines in vivo

1978 ◽  
Vol 56 (3) ◽  
pp. 535-538 ◽  
Author(s):  
S. W. Tang ◽  
H. C. Stancer ◽  
J. J. Warsh
Keyword(s):  
Central Nervous System ◽  
Animal Model ◽  
Nervous System ◽  
Specific Activity ◽  
Brain Catecholamines ◽  
Radiotracer Method ◽  
New Strategy ◽  
The Central Nervous System ◽  
6 Hydroxydopamine

A new strategy for measurement of brain catecholamines was tested in an animal model. [3H]Norepinephrine was infused intravenously in rabbits to label the peripheral norepinephrine pools. The specific activity of urinary 3-methoxy-4-hydroxymandelic acid was consistently higher than that for 3-methoxy-4-hydroxyphenylglycol (MHPG). Central sympathectomy with 6-hydroxydopamine abolished this difference. Using the formula we propose, it is estimated that 30–50% of urinary MHPG originates from the central nervous system.

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