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Glial cells – traditionally thought as simply the “glue” of the nervous system – are increasingly recognized to play a critical role in the development and function of the brain. Importantly, glial cell dysfunction has recently been shown to contribute to various neurological disorders, such as autism, schizophrenia, pain, and neurodegeneration. Understanding the function of glial cells under normal, physiological conditions, as well as how it goes awry in disease, has the potential to revolutionize how we think about the function and dysfunction of the nervous system, and inspire the development of new therapies to treat these devastating disorders.
Microglia are by far the best-characterized macrophages in the CNS, but non-parenchymal populations, such as those found in the meninges, are being increasingly studied. Prinz et al. review the ontogeny and functions of both parenchymal macrophages and non-parenchymal macrophages the CNS.
Emerging evidence suggests that astrocytes may be as diverse in their physiological and functional characteristics as neurons. Ben Haim and Rowitch describe astrocyte heterogeneity, consider the mechanisms by which such diversity may arise and discuss the consequences of its disruption in disease.
Central and peripheral inflammation can be induced by psychological stress and is associated with depressive symptoms, suggesting a possible role for immune dysfunction in depression. Duman and colleagues examine the neuroimmune mechanisms influencing neuronal–microglial interactions, neuronal activity and synaptic plasticity in stress and depression.
Dynamic membrane transformations are not exclusively controlled by cytoskeletal rearrangement, but also by biophysical constraints, adhesive forces, membrane curvature and compaction. Recent technological advances have helped clarify longstanding controversies concerning myelination, from target selection to axon wrapping and membrane compaction. Chang et al. review these findings and discuss how understanding these processes provides insight into myelination-centered mechanisms of neural plasticity.
Effective drug treatments for intracerebral haemorrhage (ICH) are still lacking. However, therapies that target microglial phenotype switching might soon become available for affected patients. Here, Wang and colleagues summarize key advances in understanding of microglial function after ICH, including modulators of microglial function and interactions with other cells.
In this Review, Salter and Stevens discuss the role of microglia in CNS disorders such as autism, neurodegenerative disorders, Alzheimer’s disease, and chronic pain.
During late-stage development, supernumerary synapses are eliminated in a process known as synaptic pruning. Here, Neniskyte and Gross give an overview of synaptic pruning in various parts of the nervous system and describe how differences in synaptic pruning may be associated with neurodevelopmental disorders.
The role of transient elevations of the intracellular concentration of calcium in astrocytes is controversial. Some neuroscientists believe that, by triggering the release of 'gliotransmitters', astrocyte calcium transients regulate synaptic strength and neuronal excitability, while others deny that gliotransmission exists. Bazargani and Attwell assess the status of this rapidly evolving field.
Tumor-associated macrophages (TAMs) establish a permissive microenvironment that positively influences glioma formation, progression and response to treatment. TAMs elaborate growth factors and cytokines that collectively facilitate tumor proliferation, survival and migration. Defining the distinct roles of these stromal cells in the glioma ecosystem may yield new opportunities for therapeutic targeting.
Reactive astrocytes have been proposed to become incompetent bystanders in epilepsy as a result of cellular changes rendering them incapable of performing housekeeping tasks. This review discusses new research that suggests that reactive astrocytes may drive the disease process by impairing the inhibitory action of neuronal GABA receptors.
In the twenty-first century, microglia came of age. Their remarkable ontogeny, unique functions and gene expression profile, process motility, and disease relevance have all been highlighted. Neuroscientists interested in microglia encounter an obsolete concept, M1/M2 polarization, suggesting experimental strategies that produce neither conceptual nor technical advances. Ransohoff's Perspective argues against applying this flawed paradigm.
This Review describes the distinct mononuclear phagocyte system (MPS) cells that are found in the different compartments of the eye. The authors discuss the importance of MPS cells for maintaining tissue homeostasis and explain how these cells contribute to eye pathology following a loss of immune privilege.
Cerebral blood flow regulation is essential for normal brain function. In this Review, Kisler and colleagues examine the cellular and molecular mechanisms that underlie cerebral blood flow regulation at the arteriole and capillary level, and how neurovascular dysfunction contributes to neurodegenerative disorders such as Alzheimer disease.
Neuroinflammation can cause acute secondary injury after traumatic brain injury (TBI), and has been linked to chronic neurodegenerative diseases; however, anti-inflammatory agents have failed to improve TBI outcomes in clinical trials. In this Review, the authors propose a new framework for targeted immunomodulation after TBI.
A series of genetic studies has implicated the microglial immune receptor TREM2 in the pathogenesis of Alzheimer disease (AD). Here, Colonna and Wang describe recent studies that have begun to unpick the mechanisms by which TREM2 is involved in AD and discuss unanswered questions in the field.
Recent studies suggest that progranulin has an important role in lysosome biogenesis and innate immunity in the brain. In this Progress article, Kao and colleagues suggest that progranulin also plays a part in suppressing excessive neuroinflammation during ageing.
The precise timing of impulse transmission along axons is crucial for synaptic plasticity and brain oscillations, and is partly determined by myelin thickness. In this Opinion article, R. Douglas Fields discusses how electrical activity influences myelin thickness and thus conduction velocity and circuit properties.