CJH332H1 Lecture Notes - Lecture 8: Myelin, Progenitor Cell, Neuroglia
Lecture 8: Re-thinking Multiple Sclerosis
- We need sodium coming in at Nodes of Ranvier but also Na-Ca exchangers
Na+ channels reorganize after injury
• Organization of the Na+ channels change after damage or injury
• High density of channels at the nodes
• Eventually loss of function as in the case of Multiple Sclerosis
• Loss of myelin/glial cell, AP does not transmit to the end of axon – disruption
• But over time, voltage gated Na channels recover and reappear so that AP is transmitted to the end
• Most of the case, this does not happen and other sodium channels degrade along with it
• NAv 1.6 (voltage gated sodium channels) have proteins (CASPR)clustered around its Node of Ranvier
- After damage, these elements that cause repeating patterns break down
- Channels are diffused after damage not in clusters
In development
• Myelinating oligodendrocyte –
myelination in CNS
- CNP, MBP, PLP, MOG
markers of oligodendrocyte
• We all have resident
oligodendrocyte precursor cells
• NG2+ glial cells
(undifferentiated) → pre-
myelinating oligodendrocyte
(precursor) → myelinating oligodendrocyte
• This process in the brain takes a week since we have so much precursor
• After damage, we can get good recovery and connectivity between the brain
A very rapid process
1. Early PSA-NCAM pre-progenitor (early OPP)
2. Late PSA-NCAM pre-progenitor (late OPP)
3. Oligodederocyte progenitor cell (OPC)
4. Pre-oligodendrocyte
5. Premyelinating oligodendrocyte
6. Myelinating oligodendrocyte
Steps in forming the node of Ranvier
• Glial processes wrap around axons to form
the myelin sheath (CNS) – can wrap multiple
• Cell body/nucleus is not myelinated (PNS)
• Astrocytic processes cuff the nodes
• Myelinated axons have four distinct domains:
node (N), paranode (PN), juxtaparanode (JPN)
and internode/axon (INT)
• Paranodes have one side with protein found on the axon and on the other, proteins found specifically in glial
cells. They come together here (like a zipper)
• Caspr are produced by axon and contactin (clustering protein)
find more resources at oneclass.com
find more resources at oneclass.com
• On glial cell membrane (from myelin), NF155 is only found on oligodendrocytes
• Paranodal loops of myelin are everted away from the axon due to a loss of junctions (transverse bands) and the
disruption of co-clustering of myelin protein NF-155 with its axonal partners Caspr/contactin as in the wild-type
mice
• Caspr allows different types if voltage gated channels to be expressed in the nodal regions
Node of Ranvier – glia and neurons
• Some proteins are expression on axons and some on oligodendrocytes
- Why we get structure of voltage gated sodium channels only in nodal regions
Things to re-visit and think about
• Schwann cells (PNS)
- Each myelin wrap have one Schwann cell
- Nucleus incorporated in myelin region
- Have underlying basal lamina allowing different activities between
PNS and CNS
• Oligodendrocytes (CNS)
- Takes processes to wrap around several different regions and
different types of neurons at the same time
- Astrocytes at different nodes of Ranvier
Is all myelin the same?
• CNS versions of myelin
- Enriched for lipophilin also called proteolipid protein-1 (PLP-1) that helps to compact myelin in CNS
- Myelin associated glycoprotein (MAG) is likely involved in the initial ensheathment (protein)
- Both peripheral and central forms of myelin contain myelin basic protein (MBP)
• PNS different series of proteins
- Myelin P0 and P2 proteins and peripheral myelin protein 22 (PMP-22)
Demyelinating disease (general)
• MS is one of the most prevalent disorders 1:500 (Canada) to 1:1000 – affects women more
- CNS – demyelination → multiple sclerosis (MS) and neuromyelitis optica (NMO)
- PNS – acute inflammatory demyelinating polyneuropathy (AIDP)
◼ Can develop antibodies for demyelination but very different for other demyelination
Multiple sclerosis
• Myelin is destructively removed from around the axon which slows down nerve impulses in a process known as
demyelination
• Axons are demyelinated in inflammatory patches called lesions
• As disease progresses, oligodendrocytes and ultimately the axons themselves are destroyed
- Relapse/remitting (get better) vs progressive (never get better)
• There is ery opellig eidee that the destrutio is aused y the ody’s o iue syste
• We do’t ko the ause!
Etiology and pathogenesis (theory)
1. Viral infection (distinct) and resulting autoimmune reaction
- Experimental allergic encephalomyelitis (EAE) animal model used
- Animals with polio injections had MS symptoms (anti-vaccine might give side effects of MS)
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
We need sodium coming in at nodes of ranvier but also na-ca exchangers. Loss of myelin/glial cell, ap does not transmit to the end of axon disruption. After damage, these elements that cause repeating patterns break down. Channels are diffused after damage not in clusters. In development: myelinating oligodendrocyte myelination in cns. A very rapid process: early psa-ncam pre-progenitor (early opp, late psa-ncam pre-progenitor (late opp, oligodederocyte progenitor cell (opc, pre-oligodendrocyte, premyelinating oligodendrocyte, myelinating oligodendrocyte. Node of ranvier glia and neurons: some proteins are expression on axons and some on oligodendrocytes. Why we get structure of voltage gated sodium channels only in nodal regions. Things to re-visit and think about: schwann cells (pns) Have underlying basal lamina allowing different activities between. Takes processes to wrap around several different regions and different types of neurons at the same time. Is all myelin the same: cns versions of myelin.
