microglial cell activation

Definition

Target type: biologicalprocess

The change in morphology and behavior of a microglial cell resulting from exposure to a cytokine, chemokine, cellular ligand, or soluble factor. [GOC:mgi_curators, PMID:10626665, PMID:10695728, PMID:12580336, PMID:9893949]

Microglial cell activation is a crucial process in the brain's immune response to injury, infection, or disease. These highly motile, phagocytic cells constantly survey the brain parenchyma, constantly adapting to changes in their environment. When an insult occurs, microglia undergo a complex transformation from a ramified, resting state to an amoeboid, activated state. This activation involves a cascade of molecular events, including:

1. **Signal Recognition:** Microglia express a vast array of pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), NOD-like receptors (NLRs), and scavenger receptors, which detect molecular patterns associated with pathogens (PAMPs) or damage-associated molecular patterns (DAMPs).

2. **Cytokine and Chemokine Release:** Upon PRR engagement, microglia release pro-inflammatory cytokines (e.g., TNF-α, IL-1β, IL-6) and chemokines (e.g., CCL2, CXCL10), which act as signaling molecules to recruit other immune cells and further amplify the inflammatory response.

3. **Phagocytosis and Debris Clearance:** Activated microglia exhibit enhanced phagocytic activity, engulfing pathogens, cellular debris, and apoptotic cells. This is crucial for removing harmful substances and restoring tissue homeostasis.

4. **Morphological Changes:** Microglial morphology shifts from a ramified, surveillance-like state to an amoeboid, phagocytic state, characterized by shortened processes and increased motility.

5. **Reactive Oxygen Species (ROS) Production:** Activated microglia produce reactive oxygen species (ROS), which serve as signaling molecules and can contribute to both beneficial and detrimental effects. ROS can be involved in pathogen killing, but excessive ROS production can lead to oxidative stress and neuronal damage.

6. **Neurotrophic Factor Release:** Microglia can also release neurotrophic factors (e.g., BDNF, GDNF), which can promote neuronal survival and regeneration. This highlights their potential role in neuroprotection and repair.

7. **Modulation of Synaptic Function:** Microglia can directly interact with synapses, contributing to synaptic plasticity and neurotransmission. In some cases, this interaction can be detrimental, leading to synaptic pruning or even synaptic loss.

8. **Resolution and Return to Resting State:** After the inflammatory stimulus is removed, microglia undergo a resolution phase, transitioning back to a resting state. This process involves downregulation of inflammatory mediators, clearance of cellular debris, and restoration of tissue homeostasis.

The activation of microglia is a complex and dynamic process. It is essential for maintaining brain health and responding to threats, but dysregulation of microglial activation can contribute to neurodegenerative diseases, stroke, and other neurological disorders.'
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Proteins (12)

Compounds (1,032)