Click on one of the other stages of microglia activation to see the molecules involved in that process. Click on Overview to see the generalized process of microglia activation during neuroinflammation.
Microglia, the immune cells of the nervous system, are typically in a quiescent, or immune-suppressed, state during normal conditions in the brain. During this time, they assume a ramified morphology, which is characterized by a very small cell body with elongated, ramified processes. These ramified microglia contribute to brain homeostasis by supporting myelin turnover, eliminating or remodeling synapses, monitoring neural firing, and actively scavenging the local environment for pathogens or tissue damage. Microglial are maintained in the ramified state through interactions with soluble and membrane-bound factors from neighboring cells. For example, Fractalkine and CD200, found on the cell surface of healthy neurons, interact with their respective receptors on microglia. These microglia receptors contain ITIM (immunoreceptor tyrosine-based inhibitory) motifs in their intracellular domain that, when phosphorylated, suppress downstream immune signaling. Additional ligand-receptor interactions that regulate microglia activation includes CD22, HSP60, and CD47 on neurons binding to CD45, TREM-2, and SIRP alpha, respectively, on microglia. Neurons also release neurotrophic factors, such as BDNF and beta-NGF, that contribute to the immune-suppressed state of microglia by inhibiting the expression of MHC class II and co-stimulatory molecules. In addition, various neurotransmitters and neuropeptides, such as GABA and dopamine, will bind to their respective receptors on microglia and suppress the production of proinflammatory cytokines. Activation of microglia is initiated, in part, following the loss of these inhibitory signals.
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