Foundations of glial biology Flashcards
LO
- Describe the timing and steps of the developmental formation of the individual glial cell types in the nervous system.
- Provide an overview of the different lineages of glial cells, and the critical factors defining lineage commitment and differentiation.
- Describe the functions played by the different glial cell types in the adult and ageing nervous system.
- Describe and give examples of critical roles of glial cells in brain disorders like Alzheimer’s disease, Multiple Sclerosis or Stroke. Discuss the contribution of glial cell activation to the progression of brain disorders.
What are the divisions of neural cells?
Neurons (10%)
Glia (90%)
With glia, what are these divided into?
Glia are 90% of the brain and of those glia, the most common are astrocytes (80%)
Most common cells in PNS are Schwann cells and those in CNS are Macroglia
Do glial cells carry nerve impulses?
Although glia cells DO NOT carry nerve impulses (action potentials) they do have many important functions. In fact, without glia, the neurons would not work properly!
What are the four main functions of glial cells?
- To surround neurons and provide physical support (hold them in place)
- To supply nutrients and oxygen to neurons (essential)
- To insulate one neuron from another and facilitate synaptic communication
- To destroy and remove cell debris and unwanted molecules
What are some other important roles that glia do?
- Glia has important developmental roles, guiding migration of neurons in early development, and producing molecules that modify the growth of axons and dendrites.
- Glia are also active participants in synaptic transmission, regulating clearance of neurotransmitter from the synaptic cleft, releasing factors such as ATP which modulate presynaptic function, and even releasing neurotransmitters themselves.
- Glia plays a fundamental role in brain disease and degeneration, defining the pathophysiological trajectory
Phylogenetical advantage of glial cells
When were Glia first notes and first named?
Glia has a long history: they were first noted in 1824 and first named in 1856. While never as studied as neurons, the early neuroscientists studied and debated glia’s classification, morphology, and roles.
Who were the main scientists involved in the discovery and identifying functions of the cells?
- glia’s ability to secrete chemicals (Nageotte)
- their association with blood vessels (Golgi)
- their morphological plasticity (Cajal)
- their ability to electrically insulate (Cajal)
- their role in neurotransmitter uptake and termination (Lugaro)
- role in pathology (Virchow).
Who is the discovery of neuroglia credited to?
The discovery of neuroglia is usually credited to Rudolf Virchow, a mid-nineteenth century German anatomist…but the first description of glia was much earlier, when French physician Rene Dutrochet noted small globules among the large globules of the mollusk nervous system in 1824.
What did Virchow do in 1856?
Virchow, in 1856, was the first to name these structures, calling them first Glia from the Greek γλία and γλοία “glue” and later “nevernkitt,” meaning nerve-glue and translated to “neuroglia.”
What role did Otto Deiters have?
Otto Deiters also had a role in the earliest descriptions of non-neuronal nervous tissue, claiming the defining feature of these new cells was their lack of axons (Some of the cells he found meeting this description were in fact incompletely stained neurons).
There is alot of debate and disagreement around classification and embryonic origins. Tell me about its ectodermic origin
Ectodermic origin: Deiters was the first to suggest this, and were thus epithelial rather than connective tissue, as Virchow thought.
What did Andriezen recognise in 1893?
Andriezen recognized two types of glia in 1893, ectodermal fibrous glia in the white matter and mesoblastic protoplasmic glia in the gray matter.
What did the father of neuroscience Ramon y Cajal think about Andriezens observation?
Ramon y Cajal agreed with the classification but argued that both came from the ectoderm.
Ramon y Cajal also noted a non-glial third element without dendrites or polarity, which probably resulted from a staining artifact.
NB: they were both astrocytes, other glia didn’t come in until later
In 1920, Pio del Rio-Hortega, a student of Cajal, classified the glia into what four types?
- protoplasmic in grey matter
- neuroglia in white matter
- mesoblastic microglia
- interfascicular glia (what are now oligodendrocytes) …what brought him a lot of trouble!
What are the neuroglia found in the PNS?
- Satellite cells
- Schwann cells
Tell me about Satellite cells
- Surround neuron in cell bodies in ganglia
- Regulates oxygen, carbon dioxide, nutrient and neurotransmitter levels around neurons in ganglia
Tell me about schwann cells
- surround axons in PNS
- are responsible for myelination of peripheral axons
- participate in repair processes after injury
What are the 5 vesicles of the brain?
What are the different stages of developent that occur in the brain and when do they occur?
What are the different cell lineages and fate choice?
What are the different stages of development from the neuroepithelial cells to the cells in the grey matter
They differentiate from neural progenitors early in development, with somata in the ventricular zone and extending prolongations to the pia
They can give rise to all cell lineages, contributing to populate the brain and providing a scaffold for neuronal migration
How do oligodendrocytes arise from the O2A progenitor?
Key stage O2A progenitor that can give rise to astrocytes and oligodendrocytes
Cells acquire identity as they migrate and colonise specific regions, defined by the factors the encounter
Oligodendrocyte differentiation is a stepwise program from NG2 precursors (retained throughout life) to mature myelinating oligodendrocytes
NG2 cells remain present in the adult brain. These could be reactivated to form more oligodendrocytes
NG2, O4 and GC
Schwann cells
Tell me about astrocytes and their stages of lineage development
Unlike OLs, the stages of astrocyte lineage development are poorly defined, lacking stage-specific markers and clearly defined developmental endpoints
Astrocyte functional heterogeneity is starting to emerge (see specific lectures), suggesting the number and role of subpopulations is yet to be defined.
Tell me about the maturation of the astrocyte population
The maturation of the astrocyte population is progressive ad mostly postnatal, generating subpopulations expressing different markers (GFAP vs S100b) and having different morphology (cortex vs hippocampus)
Disclosure: Microglia are macrophages… and only one of the brain’s immune populations
Immune census of the brain
Development and maintenance of the brain’s immune toolkit: Microglia and non-parencymal brain macrophages
Systemic sensing microglia
Brief history of microglia
1880: Nissl staining developed by Franz Nissl, allowing visualization of cells including microglia.
Nissl and Robertson first described microglial cells, showing that microglia are related to macrophages. Stābchenzellen (rod cells)
The activation of microglia and formation of ramified microglial clusters was first noted by Victor Babeş while studying a rabies case in 1897. Babeş noted the cells were found in a variety of viral brain infections but did not know what the clusters of microglia he saw were.
Pío del Río Hortega, a student of Santiago Ramón y Cajal, first called the cells “microglia” around 1920.
Rio Hortega went on to characterize microglial response to brain lesions in 1927 and note the “fountains of microglia” present in the corpus callosum and other perinatal white matter areas in 1932. After many years of research Rio-Hortega became generally considered as the “Father of Microglia”
1988, Hickey and Kimura showed that perivascular microglial cells are bone-marrow derived, and express high levels of MHC class II proteins used for antigen presentation
Microglial development… for more than 100 years…
- Rio Hortega “fountains of microglia”
- Assumed origin from circulating monocytes, until first experiments testing this hypothesis by 90’s
- Experimental models largely confounding the origin on microglia until 2010
- “Golden era” of microglial biology?
The brain is colonised directly. What does this means how does this compare to other organs?
The brain is colonised directly (without relay in the liver) and earlier than other organs
What do EMPs develop via and into what?
EMPs develop via the macrophage ancestor population A1 (CD45+, CX3CR1low, F4/80low) into the A2 (CD45+, CX3CR1hi, F4/80hi) progenitor population that commit to microglial cells
Give examples of some transcription factors which are specific or highly enriched in microglia?
Whats their roles?
Several transcription factors are specific or highly enriched in microglia, including SALL1, SALL3, MEIS3, and MAFB. However, their roles in microglia biology remain to be elucidated.
