Neuron–glia crosstalk in health and disease: fractalkine and CX3CR1 take centre stage
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TLDR
FKN appears to be neuroprotective in some settings, whereas it contributes to neuronal damage in others, and targeting CX3CR1 receptor hyperactivation with specific antagonists in such neuroinflammatory conditions may eventually lead to novel neurotherapeutics.Abstract:
An essential aspect of normal brain function is the bidirectional interaction and communication between neurons and neighbouring glial cells. To this end, the brain has evolved ligand–receptor partnerships that facilitate crosstalk between different cell types. The chemokine, fractalkine (FKN), is expressed on neuronal cells, and its receptor, CX3CR1, is predominantly expressed on microglia. This review focuses on several important functional roles for FKN/CX3CR1 in both health and disease of the central nervous system. It has been posited that FKN is involved in microglial infiltration of the brain during development. Microglia, in turn, are implicated in the developmental synaptic pruning that occurs during brain maturation. The abundance of FKN on mature hippocampal neurons suggests a homeostatic non-inflammatory role in mechanisms of learning and memory. There is substantial evidence describing a role for FKN in hippocampal synaptic plasticity. FKN, on the one hand, appears to prevent excess microglial activation in the absence of injury while promoting activation of microglia and astrocytes during inflammatory episodes. Thus, FKN appears to be neuroprotective in some settings, whereas it contributes to neuronal damage in others. Many progressive neuroinflammatory disorders that are associated with increased microglial activation, such as Alzheimer's disease, show disruption of the FKN/CX3CR1 communication system. Thus, targeting CX3CR1 receptor hyperactivation with specific antagonists in such neuroinflammatory conditions may eventually lead to novel neurotherapeutics.read more
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References
More filters
Journal ArticleDOI
Resting Microglial Cells Are Highly Dynamic Surveillants of Brain Parenchyma in Vivo
TL;DR: Using in vivo two-photon imaging in neocortex, it is found that microglial cells are highly active in their presumed resting state, continually surveying their microenvironment with extremely motile processes and protrusions.
Journal ArticleDOI
Fate Mapping Analysis Reveals That Adult Microglia Derive from Primitive Macrophages
Florent Ginhoux,Florent Ginhoux,Melanie Greter,Marylene Leboeuf,Sayan Nandi,Peter See,Solen Gokhan,Mark F. Mehler,Simon J. Conway,Lai Guan Ng,E. Richard Stanley,Igor M. Samokhvalov,Miriam Merad +12 more
TL;DR: Results identify microglia as an ontogenically distinct population in the mononuclear phagocyte system and have implications for the use of embryonically derived microglial progenitors for the treatment of various brain disorders.
Journal ArticleDOI
Chemokines: A New Classification System and Their Role in Immunity
Albert Zlotnik,Osamu Yoshie +1 more
Journal ArticleDOI
Synaptic Pruning by Microglia Is Necessary for Normal Brain Development
Rosa C. Paolicelli,Giulia Bolasco,Francesca Pagani,Laura Maggi,Maria Scianni,Patrizia Panzanelli,Maurizio Giustetto,Tiago Ferreira,Eva Guiducci,Laura Dumas,Davide Ragozzino,Cornelius Gross +11 more
TL;DR: It is shown that microglia actively engulf synaptic material and play a major role in synaptic pruning during postnatal development in mice and this work suggests that deficits in microglian function may contribute to synaptic abnormalities seen in some neurodevelopmental disorders.
Journal ArticleDOI
Physiology of Microglia
TL;DR: Current studies indicate that even in the normal brain, microglia have highly motile processes by which they scan their territorial domains, and microglial cells are considered the most susceptible sensors of brain pathology.