Lecture 11 - Glial biology II: more than just the glues Flashcards
Functions of Glial Cells
3. Myelin and the role of neuroglial cells in axonal conduction
What is a major function of oligodendrycotes and Schwann cells?
A major function of oligodendrycotes and Schwann cells is to provide the insulating material that allows rapid conduction of electrical signals along the axon. These cells produce thin sheets of myelin that wrap concentrically, many times, around the axon.
The number of layers of myelin on an axon is proportional to the diameter of the axon, i.e., larger axons have thicker sheaths. Axons with very small diameters are not myelinated. Nonmyelinated axons conduct action potentials much more slowly than do myelinated axons because of their smaller diameter and lack of myelin insulation.
Functions of Glial Cells
3. Myelin and the role of neuroglial cells in axonal conduction
How do oligodendrocytes and Schwann cells differ in the myelin produced?
Central nervous system myelin produced by oligodendrocytes is similar but not identical to
peripheral nervous system myelin produced by Schwann cells. Both types of glia produce myelin only for segments of axons. This is because the axon is not continuously wrapped in myelin, a feature that facilitates propagation of action potentials.
One Schwann cell produces a single myelin sheath for one segment of one axon, whereas one oligodendrocyte produces myelin sheaths for segments of as many as 30 axons.
Functions of Glial Cells
3. Myelin and the role of neuroglial cells in axonal conduction
Why are the myelin basic proteins positively charged?
What protein components are specific to CNS and PNS?
Phospholipid head is negatively charged, tight packing
CNS - PLP
PNS - P0
Functions of Glial Cells
3. Myelin and the role of neuroglial cells in axonal conduction
What are the characteristics and functions of myelin sheath?
The regularly spaced segments of myelin sheath are separated by unmyelinated gaps, called nodes of Ranvier, where the plasma membrane of the axon is exposed to the extracellular space approximately 1 um. This arrangement greatly increases the speed at which nerve impulses are conducted (up to 100 m/s in humans) because the signal jumps from one node to the next, a mechanism called saltatory conduction.
Nodes are easily excited because they have a low threshold. In the axon membrane at the nodes the density of Na+ channels, which generate the action potential, is approximately 50 times greater than in the myelin-sheathed regions of membrane. Several cell adhesion molecules in the paranodal regions keep the myelin boundaries stable.
What do oligodendrocytes develop from?
Oligodendrocyte precursor cells (OPCs)
Neural stem cell –> polydendrocyte (OPC) –> premyelinating oligodendrocyte –> myelinating oligodendrocyte
What do Schwann cells develop from?
Schwann cell precursors (SCPs)
Neural crest cell –> SCP –> immautre Schwann cells –> EITHER non-myelinating Schwann cell OR pro-myelin Schwann cell –> myelinating Schwann cell
More than just myelination
4. Oligodendrocytes provide metabolic support for neurons. How?
Schematic depiction of an oligodendrocyte that takes up blood-derived glucose and delivers glycolysis products (pyruvate/lactate) via monocarboxylate transporters (MCT1 and MCT2) to myelinated axons. Oligodendrocytes and myelin membranes are also coupled by gap junctions to astrocytes and, thus, indirectly to the blood-brain barrier.
How do Cre and Flp recombinase enable recombination?
What are the recombination reactions mediated?
Cre performs recombination on loxP, Flp performs recombination on FRT
Excision/insertion
Inversion
Reciprocal translocation between non-homologous chromosomes
Why is the dual-recombinase strategy preferred to the tri-lox strategy for removing selection cassette from a conditional allele?
Tri-lox strategy can result in three different types of excisions, while dual-recombinase strategy will remove only the selection cassette
More than just myelination
5. White matter plasticity for spatial and motor skill learning
What are the findings?
White matter can be modified upon learning skills. The neurons and the myelin exhibit cross-talk
Functions of Glial Cells
6. Schwann cells as pathways for outgrowth in peripheral nerves
How was this shown experimentally?
Experimental design and outcome
(a) Both end plates innervated
(b) Right end plate denervated
(c) Schwann cell sprouts from denervated end plate
(d) Uninjured axon follows Schwann cell to denervated end plate
Functions of Glial Cells
7. What is the role of microglial cells in CNS repair and regeneration?
Unlike neurons, astrocytes and oligodendrocytes, microglia do not belong to the neuroectodermal lineage. Instead they derive from yolk sac. Microglia enter the CNS early in development and they reside in all regions of CNS throughout life.
Their functions are not well understood, although they probably play an import role in immunological surveillance in CNS, poised to react to foreign invaders. Microglia are the best at processing and presenting antigens to lymphocytes and secreting cytokines and chemokines during inflammation. Thus, they serve to bring lymphocytes, neutrophils, and monocytes into CNS and expand the lymphocyte population, important immunological activities in infection, stroke, and immune-mediated demyelinating disease.
Microglia can also become macrophages clearing debris after infracts (strokes) or other degenerative neurological disorders.
Programmed cell death, phagocytosis, neuronal plasticity, synaptic pruning
Where do microglia come from?
In development, erythromyeloid progenitors (EMPs) derived from the yolk sac colonise the embryonic brain (at embryonic day 9.5 in mice, and gestational week (gw) 4.5 and 12-13 in human). Mouse studies showed these cells will express Runx1, Pu.1, Irf8, Sall1, and Sall3. These cells reach full maturation between E10.5 and birth in the mouse, and gw 22—35 in the human. In mouse, this involves expression of Csfr1, Cxcr2, Cd14, and Mafb.
What do experiments on the blood-brain barrier using dye show?
There is an impermeable barrier between blood and brain, but a permeable barrier between brain and cerebrospinal fluid
What are the anatomy and cellular constituents of the blood-brain barrier?
The endothelial cells of brain barrier contain increased numbers of mitochondria to support energy-dependent transport, capillaries are interconnected by interendothelial tight junctions. These anatomical features in conjunction with specific transport systems result in highly selective transport of water-soluble compounds across the barrier endothelium. Astroglial foot processes almost completely surround the brain capillaries. In contrast, systemic capillaries have interendothelial cleft, allowing relatively non-selective diffusion across the capillary wall.
