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Immunity Oct 2021As resident macrophages of the central nervous system (CNS), microglia are associated with diverse functions essential to the developing and adult brain during... (Review)
Review
As resident macrophages of the central nervous system (CNS), microglia are associated with diverse functions essential to the developing and adult brain during homeostasis and disease. They are aided in their tasks by intricate bidirectional communication with other brain cells under steady-state conditions as well as with infiltrating peripheral immune cells during perturbations. Harmonious cell-cell communication involving microglia are considered crucial to maintain the healthy state of the tissue environment and to overcome pathology such as neuroinflammation. Analyses of such intercellular pathways have contributed to our understanding of the heterogeneous but context-associated microglial responses to environmental cues across neuropathology, including inflammatory conditions such as infections and autoimmunity, as well as immunosuppressive states as seen in brain tumors. Here, we summarize the latest evidence demonstrating how these interactions drive microglia immune and non-immune functions, which coordinate the transition from homeostatic to disease-related cellular states.
Topics: Animals; Central Nervous System; Homeostasis; Humans; Microglia
PubMed: 34644556
DOI: 10.1016/j.immuni.2021.09.014 -
Cell Jul 2017The nervous system-in particular, the brain and its cognitive abilities-is among humans' most distinctive and impressive attributes. How the nervous system has changed... (Review)
Review
The nervous system-in particular, the brain and its cognitive abilities-is among humans' most distinctive and impressive attributes. How the nervous system has changed in the human lineage and how it differs from that of closely related primates is not well understood. Here, we consider recent comparative analyses of extant species that are uncovering new evidence for evolutionary changes in the size and the number of neurons in the human nervous system, as well as the cellular and molecular reorganization of its neural circuits. We also discuss the developmental mechanisms and underlying genetic and molecular changes that generate these structural and functional differences. As relevant new information and tools materialize at an unprecedented pace, the field is now ripe for systematic and functionally relevant studies of the development and evolution of human nervous system specializations.
Topics: Animals; Biological Evolution; Brain; Gene Expression Regulation; Language; Mutation; Nerve Tissue Proteins; Nervous System; Nervous System Physiological Phenomena; Primates; Species Specificity
PubMed: 28708995
DOI: 10.1016/j.cell.2017.06.036 -
Science (New York, N.Y.) Oct 2018Glia constitute roughly half of the cells of the central nervous system (CNS) but were long-considered to be static bystanders to its formation and function. Here we... (Review)
Review
Glia constitute roughly half of the cells of the central nervous system (CNS) but were long-considered to be static bystanders to its formation and function. Here we provide an overview of how the diverse and dynamic functions of glial cells orchestrate essentially all aspects of nervous system formation and function. Radial glia, astrocytes, oligodendrocyte progenitor cells, oligodendrocytes, and microglia each influence nervous system development, from neuronal birth, migration, axon specification, and growth through circuit assembly and synaptogenesis. As neural circuits mature, distinct glia fulfill key roles in synaptic communication, plasticity, homeostasis, and network-level activity through dynamic monitoring and alteration of CNS structure and function. Continued elucidation of glial cell biology, and the dynamic interactions of neurons and glia, will enrich our understanding of nervous system formation, health, and function.
Topics: Animals; Cell Movement; Central Nervous System; Mice; Neurogenesis; Neuroglia; Neuronal Plasticity; Neurons; Synapses; Synaptic Transmission
PubMed: 30309945
DOI: 10.1126/science.aat0473 -
Nature Reviews. Neuroscience Nov 2021The sympathetic nervous system prepares the body for 'fight or flight' responses and maintains homeostasis during daily activities such as exercise, eating a meal or... (Review)
Review
The sympathetic nervous system prepares the body for 'fight or flight' responses and maintains homeostasis during daily activities such as exercise, eating a meal or regulation of body temperature. Sympathetic regulation of bodily functions requires the establishment and refinement of anatomically and functionally precise connections between postganglionic sympathetic neurons and peripheral organs distributed widely throughout the body. Mechanistic studies of key events in the formation of postganglionic sympathetic neurons during embryonic and early postnatal life, including axon growth, target innervation, neuron survival, and dendrite growth and synapse formation, have advanced the understanding of how neuronal development is shaped by interactions with peripheral tissues and organs. Recent progress has also been made in identifying how the cellular and molecular diversity of sympathetic neurons is established to meet the functional demands of peripheral organs. In this Review, we summarize current knowledge of signalling pathways underlying the development of the sympathetic nervous system. These findings have implications for unravelling the contribution of sympathetic dysfunction stemming, in part, from developmental perturbations to the pathophysiology of peripheral neuropathies and cardiovascular and metabolic disorders.
Topics: Animals; Axons; Dendrites; Humans; Neuronal Plasticity; Neurons; Peripheral Nervous System Diseases; Sympathetic Nervous System
PubMed: 34599308
DOI: 10.1038/s41583-021-00523-y -
Acta Neuropathologica Jan 2010Astrocytes are specialized glial cells that outnumber neurons by over fivefold. They contiguously tile the entire central nervous system (CNS) and exert many essential... (Review)
Review
Astrocytes are specialized glial cells that outnumber neurons by over fivefold. They contiguously tile the entire central nervous system (CNS) and exert many essential complex functions in the healthy CNS. Astrocytes respond to all forms of CNS insults through a process referred to as reactive astrogliosis, which has become a pathological hallmark of CNS structural lesions. Substantial progress has been made recently in determining functions and mechanisms of reactive astrogliosis and in identifying roles of astrocytes in CNS disorders and pathologies. A vast molecular arsenal at the disposal of reactive astrocytes is being defined. Transgenic mouse models are dissecting specific aspects of reactive astrocytosis and glial scar formation in vivo. Astrocyte involvement in specific clinicopathological entities is being defined. It is now clear that reactive astrogliosis is not a simple all-or-none phenomenon but is a finely gradated continuum of changes that occur in context-dependent manners regulated by specific signaling events. These changes range from reversible alterations in gene expression and cell hypertrophy with preservation of cellular domains and tissue structure, to long-lasting scar formation with rearrangement of tissue structure. Increasing evidence points towards the potential of reactive astrogliosis to play either primary or contributing roles in CNS disorders via loss of normal astrocyte functions or gain of abnormal effects. This article reviews (1) astrocyte functions in healthy CNS, (2) mechanisms and functions of reactive astrogliosis and glial scar formation, and (3) ways in which reactive astrocytes may cause or contribute to specific CNS disorders and lesions.
Topics: Animals; Astrocytes; Central Nervous System; Central Nervous System Diseases; Humans; Models, Neurological
PubMed: 20012068
DOI: 10.1007/s00401-009-0619-8 -
Annual Review of Immunology Apr 2018The nervous system regulates immunity and inflammation. The molecular detection of pathogen fragments, cytokines, and other immune molecules by sensory neurons generates... (Review)
Review
The nervous system regulates immunity and inflammation. The molecular detection of pathogen fragments, cytokines, and other immune molecules by sensory neurons generates immunoregulatory responses through efferent autonomic neuron signaling. The functional organization of this neural control is based on principles of reflex regulation. Reflexes involving the vagus nerve and other nerves have been therapeutically explored in models of inflammatory and autoimmune conditions, and recently in clinical settings. The brain integrates neuro-immune communication, and brain function is altered in diseases characterized by peripheral immune dysregulation and inflammation. Here we review the anatomical and molecular basis of the neural interface with immunity, focusing on peripheral neural control of immune functions and the role of the brain in the model of the immunological homunculus. Clinical advances stemming from this knowledge within the framework of bioelectronic medicine are also briefly outlined.
Topics: Animals; Biomarkers; Disease Susceptibility; Humans; Immunity; Nervous System; Nervous System Physiological Phenomena; Neuroimmunomodulation; Signal Transduction; Translational Research, Biomedical
PubMed: 29677475
DOI: 10.1146/annurev-immunol-042617-053158 -
Nutrients Jun 2018Magnesium is well known for its diverse actions within the human body. From a neurological standpoint, magnesium plays an essential role in nerve transmission and... (Review)
Review
Magnesium is well known for its diverse actions within the human body. From a neurological standpoint, magnesium plays an essential role in nerve transmission and neuromuscular conduction. It also functions in a protective role against excessive excitation that can lead to neuronal cell death (excitotoxicity), and has been implicated in multiple neurological disorders. Due to these important functions within the nervous system, magnesium is a mineral of intense interest for the potential prevention and treatment of neurological disorders. Current literature is reviewed for migraine, chronic pain, epilepsy, Alzheimer’s, Parkinson’s, and stroke, as well as the commonly comorbid conditions of anxiety and depression. Previous reviews and meta-analyses are used to set the scene for magnesium research across neurological conditions, while current research is reviewed in greater detail to update the literature and demonstrate the progress (or lack thereof) in the field. There is strong data to suggest a role for magnesium in migraine and depression, and emerging data to suggest a protective effect of magnesium for chronic pain, anxiety, and stroke. More research is needed on magnesium as an adjunct treatment in epilepsy, and to further clarify its role in Alzheimer’s and Parkinson’s. Overall, the mechanistic attributes of magnesium in neurological diseases connote the macromineral as a potential target for neurological disease prevention and treatment.
Topics: Brain; Central Nervous System Agents; Central Nervous System Diseases; Humans; Magnesium; Prognosis; Spinal Cord
PubMed: 29882776
DOI: 10.3390/nu10060730 -
The Journal of Experimental Medicine Apr 2020The blood vessels vascularizing the central nervous system exhibit a series of distinct properties that tightly control the movement of ions, molecules, and cells... (Review)
Review
The blood vessels vascularizing the central nervous system exhibit a series of distinct properties that tightly control the movement of ions, molecules, and cells between the blood and the parenchyma. This "blood-brain barrier" is initiated during angiogenesis via signals from the surrounding neural environment, and its integrity remains vital for homeostasis and neural protection throughout life. Blood-brain barrier dysfunction contributes to pathology in a range of neurological conditions including multiple sclerosis, stroke, and epilepsy, and has also been implicated in neurodegenerative diseases such as Alzheimer's disease. This review will discuss current knowledge and key unanswered questions regarding the blood-brain barrier in health and disease.
Topics: Animals; Biological Transport; Blood-Brain Barrier; Central Nervous System; Humans
PubMed: 32211826
DOI: 10.1084/jem.20190062 -
Trends in Molecular Medicine Nov 2019Originally hypothesized to function solely as immunologic responders within the central nervous system (CNS), emerging evidence has revealed that microglia have more... (Review)
Review
Originally hypothesized to function solely as immunologic responders within the central nervous system (CNS), emerging evidence has revealed that microglia have more complex roles in normal brain development and in the context of disease. In health, microglia influence neural progenitor fate decisions, astrocyte activation, neuronal homeostasis, and synaptogenesis. In the setting of brain disease, including autism, brain tumors, and neurodegenerative disorders, microglia undergo substantial morphological, molecular, and functional changes, which establish new biological states relevant to disease pathogenesis and progression. In this review, we discuss the function of microglia in health and disease and outline a conceptual framework for elucidating their specific contributions to nervous system pathobiology.
Topics: Aging; Animals; Astrocytes; Autistic Disorder; Biomarkers; Brain; Brain Neoplasms; Cell Differentiation; Cellular Microenvironment; Central Nervous System; Homeostasis; Humans; Inflammation Mediators; Microglia; Neurodegenerative Diseases; Neurons; Synapses
PubMed: 31597593
DOI: 10.1016/j.molmed.2019.08.013 -
Cell Chemical Biology May 2020Over the past five decades, thanatology has come to include the study of how individual cells in our bodies die appropriately and inappropriately in response to... (Review)
Review
Over the past five decades, thanatology has come to include the study of how individual cells in our bodies die appropriately and inappropriately in response to physiological and pathological stimuli. Morphological and biochemical criteria have been painstakingly established to create clarity around definitions of distinct types of cell death and mechanisms for their activation. Among these, ferroptosis has emerged as a unique, oxidative stress-induced cell death pathway with implications for diseases as diverse as traumatic brain injury, hemorrhagic stroke, Alzheimer's disease, cancer, renal ischemia, and heat stress in plants. In this review, I highlight some of the formative studies that fostered its recognition in the nervous system and describe how chemical biological tools have been essential in defining events necessary for its execution. Finally, I discuss emerging opportunities for antiferroptotic agents as therapeutic agents in neurological diseases.
Topics: Animals; Central Nervous System; Drug Discovery; Ferroptosis; Humans; Nervous System Diseases; Oxidative Stress
PubMed: 32243811
DOI: 10.1016/j.chembiol.2020.03.007