Lecture 14- The Role of Glial Cells in the Brain 2 Flashcards
What are microglia like in terms of their structure?
Small + highly branched (look like astrocytes but smaller)
How much percentage of glial cells do microglia make up?
5-20%
Are microglia easy or difficult to identify?
- Difficult as cannot use Nissl or Golgi stains
- Use Immuno-cytochemical identification based on Iba1 - actin binding proteins (binds up calcium)
What are the functions of microglia?
- homeostasis – routinely monitor extracellular environment
- activity dependent synapse elimination (ones that are no longer functional or are hyperactive)
- phagocytosis (eat+ destroy) of surplus neural precursor cells
- defence function -> normal (-> exacerbate inflammation)
- many roles in disease processes
What is the distribution of microglia like? What type of matter are they more commonly found in?
- Regional variation
- More in grey matter (near neuronal soma)
- Near synapses
- Concomittant with astrocytes
Are all microglia the same?
No, there is large phenotypic variability
What are the two broad classes of functions for microglia?
- Immune functions: phagocytosis, antigen presentation, Cytokine and chemokine production, pro-inflammatory or anti-inflammatory response, immuno-surveillance through extra and intracellular receptors
- Neuronal functions: Neurogenesis, induction of apoptosis, phagocytosis of apoptotic neurons, maintenance of neuronal health, synaptic pruning, circuit formation and maturation, can effect basal transmission and synaptic plasticity (LTP).
What is synaptic pruning? What condition results when this process goes wrong?
- Born with way to many synapses, development involves synaptic pruning (Destruction).
- Neurons are energy extensive cause make lot of proteins therefore, don’t want a whole bunch around that aren’t needed
- Synaptic pruning is key to maintaining synaptic circuits
- Autism is this when goes wrong- it doesn’t occur so too many synapses are maintained and this leads to information overload.
How do microglia develop (what is there morphology)?
- Myeloid lineage : this is what makes them distinct from other cells and why they can have immune functions
- Develop from haemopoietic cells of the bone marrow
- Invade the CNS in late embryonic development
What is the morphology of microglia like in adults?
- In adult variable shape- dependent on function and due to rearrangement of actin cytoskeleton
- Can divide (mitosis)
- Renew slowly (-30%/year) , microglia can last 20 + years
What are the three different shapes microglia come in according to their function?
- Ramified= homeostasis, surveillance, monitoring
- Bushy= Neurodegeneration, inflammation, toxicity
- Amoeboid= phagocytosis, inflammation, motility
Iba1 intensity increases as go down this list!
What do microglia look like in under a microscope?
- elongated nuclei “bean” shaped with peripheral heterochromatin
- scattered cisternae of rough endoplasmic reticulum and Golgi complexes at both poles
- If a microglial cell is adjacent to a neuron there is usually a thin astrocytic process (arrow)
What progression for microglia occurs going from rest to activation?
Resting: Not moving - but Ramified (branched) processes survey the microenvironment
Activated: Amoeboid. Move freely throughout neural tissue. Have function of Phagocytosing debris and Pruning cells/dendrites.
Why are we interested in microglia function/ what can happen when microglial malfunction?
- When at rest the microglia act to survey/ check everything is okay, when injury occurs receptors in the microglial cell membrane detect and call for backup/ initiate a response
- Hyperactive microglia has been linked to Alzheimer’s
What happens in the microglia injury response?
- Synthesis and release of chemokines: attract other microglia
- Proliferation or entry of monocytes via BBB (often faulty in disease)
- Become motile, apoptosis, phagocytic
