3: Glial Cells and BBB Flashcards
(17 cards)
What are the stages of CNS development?
1) Neurogenesis: division of non-neuronal cells (stem and precursor cells) to produce neurons
2) Cell migration: movement of cells to establish distinct neuronal cell populations
3) Differentiation: formation of distinct neurons or glia (during migration)
4) Synaptogenesis: establishment of synaptic contacts (axons and dendrites grow)
5) Neuronal cell death: selective death of many neurons
6) Synapse rearrangement: loss of some synapses and development of others; refine synaptic connections
What are neuroepithelial cells?
- neuroepithelial cells are precursor cells that surround the ventricular zone (filled with stem cells)
- proliferate and generate neuroblasts and immature neurons.
- They then differentiate into radial glia which proliferate and elongate
- neuroepithelial cells later form the BBB
What are radial glial cells?
- Differentiate (come from) from neuroepithelial cells in the developing CNS
- -These radial glial cells then set up the tracts from the ventricular zone (central canal) to the pial surface (cortex) for neurons to follow along to get out and build the cortex (act as a scaffold for neuronal migration) and provide structural support during axon growth
- growth cones (from newly formed neurons in the ventricular zone) grab onto those radial glial cells and pull and travel to the cortex and other regions (scaffolding)
- after the neurodevelopmental process is over, these radial glial cells pull themselves up from the ventricular zone to the cortex
- They then serve as primary progenitor cells capable of generating neurogenesis and gliogenesis (astrocytes/oligodendrocytes); contribute to neurogenesis directly or via immediate neuronal precursor cells (nIPC) after they have done their job in cell migration
- as well as produce intermediate progenitors that expand in number before producing astrocytes
- Some radial glia may also differentiate into ependymal cells which line the ventricles of the adult CNS
What are astrocytes?
- control extracellular K+ homeostasis (extra K+ floating around in the extracellular environment after the Na-K pump gets taken up)
- remove excess glutamate to reduce excitation (and pump it back into the neuron)
- supply glutamine to maintain glutamatergic neurotransmission
- control local blood flow and provide neurons with metabolic support (glucose from blood get taken up by the astrocytes which can then be fed to the neuron)
- control synaptogenesis and synaptic maintenance
What are protoplasmic astrocytes?
- Present in gray matter
- Have many fine processes (approx ~50 µm long), which are extremely elaborate and complex;
- ‘perivascular’ endfeet (around blood vessels): these processes contact blood vessels and form multiple contacts with neurons.
- ‘subpial’ endfeet (beneath Pia mater): Some protoplasmic astrocytes also send processes to the pial surface
What are fibrous astrocytes?
- Present in white matter
- Their processes are long (up to 300 µm), though much less elaborate as compared to protoplasmic astroglia
- ‘perinodal’ processes: extensions that contact axons at nodes of Ranvier
- perivascular or subpial (beneath Pia mater) endfeet
Where does myelin cover the axon?
- Myelin covers the axon at intervals (internodes), leaving bare gaps — the nodes of Ranvier (span less than 1 micron)
- Myelinating glial cells, oligodendrocytes in the central nervous system (CNS) or Schwann cells in the peripheral nervous system (PNS), form the myelin sheath by enwrapping their membrane several times around the axon
What are Schwann cells?
- Form myelin around fast conducting axons in the peripheral nerves and ganglia
- They can also enclose smaller axons (less than 1 um in diameter) without forming a myelin sheath (are encased by Schwann cell cytoplasm, but there is no wrapped coating of myelin surrounding the axons)
- Associated with only one axonal segment (one Schwann cell for one axon)
- While central and peripheral myelin share the basic protein myelin, the peripheral nervous system lacks myelin associated glycoprotein or proteolipid protein
- Immature Schwann cells produce either myelinating or non-myelinating Schwann cells. The latter loosely enwraps several axons without forming myelin
Where are Schwann cells derived from?
– Schwann cells are derived from undifferentiated migrating neural crest cells
How is pain different for myelinated vs unmyelinated neurons?
> Myelinated SC: sodium comes up which spikes the action potential (saltatory conduction) –initial pain
Non-myelinated SC: continuous conduction –slow, dull pain
What are oligodendrocytes?
- All white matter tracts contain oligodendrocytes to form myelin
- While oligodendrocytes are very well known as the myelin forming cells of the central nervous system there are also oligodendrocytes that are not directly connected to the myelin sheath
- Nonmyelinating oligodendrocytes (a) are preferentially found in gray matter and have so far unknown functions possibly serving to regulate ionic homeostasis similarly to astrocytes.
- Myelin forming oligodendrocytes have several processes (up to 40) which connect to one myelin segment.
- Each of these segments is several hundred micrometers long and is also termed the internode.
- Segments are interrupted by structures known as node of Ranvier which spans for less than 1 micron (not enwrapped by myelin)
- The end of intermodal segment contains more cytoplasm and forms so called paranodal loop creating septate, like junctions with the axon
- In addition, astrocyte processes contact the axonal membrane at the nodal region (node of ranvier)
What are microglia?
- Microglial cells derive from progenitors that have migrated from the periphery and are from mesodermal/ mesenchymal origin
- After invading the CNS, microglial precursors disseminate relatively homogeneously throughout the neural tissue
- Acquire a specific phenotype, which clearly distinguish them from their precursors, the blood-derived monocytes (macrophages)
- Traditional role in brain infection and disease, phagocytosing debris and secreting factors to modify disease progression (pro-inflammatory cytokines which trigger the immune response and help the disease, or worsen it)
- Recent role in healthy brain homeostasis, including the regulation of cell death, synapse elimination, neurogenesis, and neuronal surveillance
- Actions contribute to the maturation and plasticity of neural circuits that ultimately shape behavior
What is the M1-like phenotype of microglia?
- The Dark Side of Microglia; Inflammatory microglia display the M1-like phenotype and stimulate astrocyte activation, neuronal damage, releases proinflammatory factors, oxidative stress, immune stimulation which can destroy the BBB and allow the peripheral immune response (t-cells, macrophages, etc) to enter the brain
- neuroinflammation and subsequent neuronal loss
What is the M2-like phenotype of microglia?
– Microglia displaying the anti-inflammatory M2-like phenotype attenuate inflammatory and neurotoxic effects induced by M1-like microglia, supporting neuronal survival, restricting BBB permeability and promoting tissue repair
What is the blood-brain barrier?
- A highly selective semipermeable membrane barrier that separates the circulating blood from the brain and extracellular fluid in the central nervous system (CNS)
- formed by brain endothelial cells and it allows the passage of water, some gases, and lipid-soluble molecules by passive diffusion, as well as the selective transport of molecules such as glucose and amino acids that are crucial to neural function
What are the different parts/functions of the BBB?
- -The continuous tight junctions that join endothelial cells in brain capillaries limit the diffusion of large and small solutes across the blood—brain barrier
- The basement membrane provides structural support for the capillary and, along with the astrocytic foot processes that encircle the capillary, may influence endothelial cell function
- Transport carriers for glucose and essential amino acids facilitate the movement of these solutes into brain
- Secondary transport systems (5) appear to cause the efflux of small, nonessential amino acids from brain to blood
- Sodium ion transporters on the luminal membrane and Na-K-ATPase on the antiluminal membrane account for the movement of sodium from blood to brain, and this may provide an osmotic driving force for the secretion of interstitial fluid by the brain capillary
What happens if you have an autoimmunity to myelin components?
excitotoxic oligodendroglial death and demyelinating diseases
– Autoimmunity to myelin components ultimately results in the activation of microglia that can release glutamate and tumor necrosis factor α (TNFα), and produce reactive oxygen and nitrogen species. These mechanisms can in turn generate various fatal feedbacks that kill oligodendrocytes and destroy myelin.
