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Microglia are resident immune cells that play critical roles in maintaining the normal physiology of the central nervous system (CNS). Remarkably, microglia have an intrinsic capacity to repopulate themselves after acute ablation. However, the underlying mechanisms that drive such restoration remain elusive. Here, we characterized microglial repopulation both spatially and temporally following removal via treatment with the colony stimulating factor 1 receptor (CSF1R) inhibitor PLX5622. We show that microglia were replenished via self-renewal, with no contribution from nonmicroglial lineages, including Nestin+ progenitors and the circulating myeloid population. Interestingly, spatial analyses with dual-color labeling revealed that newborn microglia recolonized the parenchyma by forming distinctive clusters that maintained stable territorial boundaries over time, indicating the proximal expansive nature of adult microgliogenesis and the stability of microglia tiling. Temporal transcriptome profiling at different repopulation stages revealed that adult newborn microglia gradually regain steady-state maturity from an immature state that is reminiscent of the neonatal stage and follow a series of maturation programs, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation, interferon immune activation, and apoptosis. Importantly, we show that the restoration of microglial homeostatic density requires NF-κB signaling as well as apoptotic egress of excessive cells. In summary, our study reports key events that take place from microgliogenesis to homeostasis reestablishment.
This article was published in the following journal.
Name: PLoS biology
In the last decade, tremendous progress has been made in understanding the biology of microglia - i.e. The fascinating immigrated resident immune cell population of the central nervous system (CNS). R...
Inflammation is a major contributor to stroke pathology, making it a promising strategy for intervention. Microglia, the resident macrophages in the brain, play essential roles in both the generation ...
Microglia, a type of glia within the brain characterized by a ramified morphology, are essential for removing neuronal debris and restricting the expansion of a lesion site. Upon moderate activation, ...
Microglia, the resident immune cells of the brain, can acquire various cell phenotypes based on their location and current role. This level of plasticity is required to fulfil the vast variety of func...
Microglia, the resident immune cells of the brain, rapidly change states in response to their environment, but we lack molecular and functional signatures of different microglial populations. Here, we...
PET imaging of activated microglia offers a tool of investigation of a range of brain diseases where neuroinflammation is a component. Amyotrophic lateral sclerosis is the most frequent m...
The overall goal of this protocol is to evaluate microglial activation in the brain using [18F]PBR06 in patients with amyotrophic lateral sclerosis (ALS).
Patients with schizophrenia have volume loss in gray matter. This study is designed to evaluate whether their is microglia activation in schizophrenia using [11C](R)-PK11195 PET.
The main objective of this study is to compare microglia activation as measured with PET in combination with the tracer [11C]-R-PK11195 between recent-onset schizophrenia patients who are ...
To evaluate the effect of teriflunomide treatment on microglial activation in late stage multiple sclerosis.
The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling.
A sodium-hydrogen antiporter expressed primarily by EPITHELIAL CELLS in the kidneys, it localizes to the apical membrane of the PROXIMAL KIDNEY TUBULE, where it functions in sodium and water reabsorption and possibly calcium homeostasis. It also is expressed in heart, brain, and lung tissues and is resistant to AMILORIDE inhibition.
The renal tubule portion that extends from the BOWMAN CAPSULE in the KIDNEY CORTEX into the KIDNEY MEDULLA. The proximal tubule consists of a convoluted proximal segment in the cortex, and a distal straight segment descending into the medulla where it forms the U-shaped LOOP OF HENLE.
Self-renewing cells that generate the main phenotypes of the nervous system in both the embryo and adult. Neural stem cells are precursors to both NEURONS and NEUROGLIA.
A cartilage-capped benign tumor that often appears as a stalk on the surface of bone. It is probably a developmental malformation rather than a true neoplasm and is usually found in the metaphysis of the distal femur, proximal tibia, or proximal humerus. Osteochondroma is the most common of benign bone tumors.
Neurology - Central Nervous System (CNS)
Alzheimer's Disease Anesthesia Anxiety Disorders Autism Bipolar Disorders Dementia Epilepsy Multiple Sclerosis (MS) Neurology Pain Parkinson's Disease Sleep Disorders Neurology is the branch of me...
Pediatrics is the general medicine of childhood. Because of the developmental processes (psychological and physical) of childhood, the involvement of parents, and the social management of conditions at home and at school, pediatrics is a specialty. With ...