Microglia

What are microglia, and what type of cell are they classified as?

Microglia are the resident immune cells of the nervous system. They are a type of macrophage (macro = large, phage = eater). They are the brain's dedicated immune sentinels

How does the developmental origin of microglia differ from neurons, astrocytes, and oligodendrocytes?

Neurons, astrocytes, and oligodendrocytes all arise from neural precursors (neural origin). Microglia are the exception — they migrate into the brain via the blood during embryonic development and are more closely related to peripheral macrophages than to other brain cells

Where else in the body are macrophages found, and what does this tell us about microglia?

Macrophages are found in the skin, liver, and lungs. Since microglia are brain macrophages, they share the same lineage as these peripheral immune cells — meaning microglia are functionally immune cells, not neural support cells

What is the resting (healthy) morphological state of microglia called, and what does it look like

Ramified. In this state, microglia have a small cell body with long, highly branched processes extending outward. These processes constantly survey the surrounding brain environment.

What is microgliosis, and what morphological changes occur during it

Microgliosis is the highly activated state of microglia triggered by injury or disease. During microgliosis, microglia retract their processes, become larger in size, take on an amoeboid shape, and begin to divide.

List the four morphological states of microglia from least to most activated

1. Ramified — healthy, highly branched, surveying

2. Intermediate — mild activation, partially retracted

3. Amoeboid — highly activated, phagocytic

4. Round — most activated stat

What does 'phagocytosis' mean, and what is an example of microglia performing it

Phagocytosis = the phenomenon where a cell eats (engulfs and destroys material). Example: in mice losing myelin due to disease, microglia phagocytose myelin debris — clearing it so remyelination can potentially occur.

Why is microglial phagocytosis of myelin debris potentially both beneficial and harmful

Beneficial: myelin debris contains signals that inhibit OPC differentiation and remyelination — clearing it opens the way for repair. Harmful: if overactivated or misdirected, microglia can engulf healthy myelin or neurons, worsening damage

What is the P2Y12 receptor on microglia, and what molecule does it bind

P2Y12 is a receptor expressed on microglia that binds ADP (adenosine diphosphate). ADP is produced by the hydrolysis of ATP. P2Y12 allows microglia to detect ADP released from damaged or overactive cells

In Eyo 2014, P2Y12 KO mice had faster seizure onset than wildtype after kainic acid. What does this tell us about the normal role of P2Y12 signaling

It shows P2Y12 signaling is neuroprotective. Normally, overactive neurons release ADP, which binds P2Y12 on microglia, triggering a response that dampens excessive neuronal excitability and delays seizure onset. Without P2Y12, this protection is lost

QUESTION In Haynes 2006, wildtype microglia converged toward a focal laser injury by 40 min, but P2ry12-/ microglia did not converge even by 120 min. What does this reveal

Damaged cells release ADP into the extracellular space, forming a chemical gradient. Microglia follow this gradient via P2Y12 (chemotaxis). Without P2Y12, microglia cannot sense the damage signal and fail to navigate toward the injury site

Name at least six functions of microglia according to the Paolicelli 2022 figure

1. Surveillance 2. Phagocytosis 3. Release of soluble factors 4. Synapse remodeling (synaptic pruning) 5. Neurogenesis support 6. Myelination 7. Inflammation regulation 8. Vasculogenesis 9. BBB permeability regulation 10. Tissue repair

What is synaptic pruning, and which cell type performs it

Synaptic pruning is the elimination of specific synapses by engulfing them — microglia use their phagocytic machinery to remove weak, redundant, or tagged synapses. This shapes neural circuit connectivity during development and maintains plasticity in adulthood

Why is it significant that microglia divide during microgliosis

Dividing allows the local microglial population to rapidly expand right at the site of injury or infection — amplifying the immune response where it is needed without requiring new cells to be recruited from the blood, which would require breaching the blood-brain barrier

How does microglial morphology vary across species, and what might this reflect

Simpler organisms (e.g., leech, zebrafish) have morphologically simpler microglia; more complex organisms (e.g., primates, humans) have more elaborate microglial morphology. This likely reflects the need to survey and regulate increasingly complex neural architectures

What marker is used to identify microglia, as seen in the Eyo 2014 and Haynes 2006 experiments

Iba1 is the canonical microglial marker used across species. In the experimental images, green fluorescence marks microglia (via GFP or Iba1 labeling), allowing their morphology and movement to be tracked in living or fixed tissue

How do microglia and astrocytes differ in their response to TBI — what does each cell type specifically do?

Microglia: enter microgliosis, become amoeboid, phagocytose debris, release inflammatory signals, survey for further damage. Astrocytes: undergo reactive astrogliosis, upregulate GFAP, attempt to maintain BBB integrity, use AQP4 at endfeet to drive glymphatic clearance of toxic proteins like tau

What is kainic acid (kainate), and why was it used in the Eyo 2014 experiment

Kainic acid is the ligand for the kainate receptor. Overactivation of the kainate receptor causes seizures. It was used to experimentally induce seizures in mice so researchers could study how P2Y12 signaling in microglia affects the brain's response to excessive neuronal activity