Sophie Flashcards
in which nervous system are microglia found?
CNS
What are microglia?
● Immune cells of the brain!
○ Non-neuronal
○ Resident macrophage of the CNS
○ They act as an innate immune cell
with memory
● Make up 7-10% of CNS cells
● First glia cell to be derived during
development
■ Prior to E8.5
Where do microglia come from?
● Most CNS cell types derive from the
neuroectoderm (Kandel, 2013)
● Microglia have a
mesodermal/mesenchymal origin
○ Develop in the yolk sac
■ Myeloid progenitors
● RUNX1
● PU.1
■ CSF1R
From and to where do microglia migrate
● Migrate to the CNS
○ Migrate as macrophages
without initial monocyte
transition
○ Migrate via the circulatory
system
○ Immature microglia, less
ramified
How do microglia differ from other macrophages?
● Microglia:
○ Derive from the fetal yolk sac
○ Residence in the brain
○ Mature microglia express
macrophage markers but
additionally have P2Y12 and
TMEM19
● Tissue macrophages:
○ Derive from bone marrow
○ Macrophages express CD206 and
CD45
What is the purpose of microglia?
● Main functions of
microglia:
○ Immune defense
○ Brain development and
function
○ Maintenance of CNS
homeostasis
■ (Ginhoux & Prinz, 2015)
How do microglia work?
- Rapidly clear dead cells, pathogens,
and debris in the brain
a. Phagocytose - Respond to injury
a. Neuroinflammation:
i. Release cytokines
make note of IL-6, TNF-alpha and C1q
Resiliency
Microglia are resilient!
● Renew slowly over time
○ around 28%/year
○ Different from other hematopoietic
lineages
● Long-lived
○ Up to 20 years
● No large population of quiescent long-lived
progenitors
Extensive Sensome
● Large sensome:
○ Many different possible
environmental insults to the
brain:
■ Infection, degeneration,
pH changes, ECM
changes, or changes in
metabolites
○ Microglia need to be able to
sense all of these!
● Neuronal sensors
● Age-related changes:
○ Genes for sensing endogenous ligands become downregulated
○ Genes for sensing exogenous (pathogenic) ligands become upregulated
- Dynamic & Mobile!
● At “rest”, microglia are highly
ramified with a small cell body
○ Cell bodies are stationary
○ Dynamic processes
● During injury and disease:
○ Become highly mobilized
■ Migrate to site
Plasticity
● Undergo morphological and genetic changes
dependent on insults and brain states:
○ Disease type, injury, age
Forms of microglia
- Ramified
a. “Resting” state
b. Continually surveying the
environment
c. Long, branching processes - Activated (Reactive)
a. Large soma
b. Retracts processes
i. “Ameboid”
ii. Can phagocytose
iii. Can release
inflammatory factors
Forms of Microglia image
Microglia in development
● Aid in the formation and maturation of synapses:
○ Neuronal proliferation, migration, and differentiation (Mosser et al, 2017)
● Develop alongside neurons:
■ Highly involved in neuronal developmental processes (Nayak et al,
2014)
● Clears apoptotic neurons
■ Amoeboid morphology
■ Cleanup unwanted synaptic circuitry
● Failure of function: Neurodevelopmental disorders
Microglia in development image
