NEUS 609 - Oligodendrocytes & Myelin II

30

Oligodendrocytes are the myelinating cells of the CNS & can myelinate up to __ axon segments

1:1

Schwann cells are the myelinating cells of the PNS & can only myelinate using a ___ ratio of cell to axon

saltatory

myelin allows propagation of action potential in a ___/discontinuous fashion

• faster than unmyelinated axons (several hundred folds faster)

• allows large vertebrate size keeping PSC thin enough

• improve space and metabolic efficiency

high, low

myelin is an insulator with a very ___ resistance, and ___ capacitance.

internode

part of myelinated axon corresponding to A SINGLE MYELINATED SEGMENT made of both compact and non-compact myelin.

node of Ranvier

small part of axon that is UNMYELINATED and located between 2 internodes.

• contains most of the voltage-gated Na+ channels

g ratio

___ = axon diameter/total fiber diameter

myelin thickness is highly correlated with axonal diameter

spiral wrapping

myelin sheath formed by ___ of an extended plasma membrane that then compacts.

intraperiod line

wide apposition of the external faces of the membrane of the myelinating cell.

major dense line

thin apposition of the internal faces of the myelinating cell membrane that have been compacted.

Schmidt-Lanterman incisures

Located in the PNS

internal/cytoplasmic faces that have not compacted and form cytoplasmic channels

• rare in CNS

Cytoplasmic channels

Located int he CNS

System of cytoplasmic channels thought to connect the oligodendrocyte cell body and the INNERMOST layer of the myelin sheath

Paranodal loops

lateral ends of the myelin internode

• attach to axon via CASPR proteins

Septin filaments

Located in the CNS

stabilizing filaments that are localized to the non-compacted adaxonal myelin compartment

• stabilizing attachment of myelin to axon

• happens at late stage of maturation

radial components

Located in CNS

Intralamellar junctional complexes that resemble tight-junctions (reduced or no spacing between extracellular surfaces of the membrane)

• generate electricity tight barrier aka insulating

• KO interferes with conduction velocity

high

CNS myelin has a ___ lipid composition made of mainly:

• cholesterol

• glycosphingolipids

• phospholipids

80

___% of proteins in myelin are MBP or PLP

myelin basic protein

aka MBP

family of proteins from which most common membrane isoforms are 14 and 18.5 kDa & are generated by alternative splicing of encoded genes on chromosome 18.

• located on CYTOSOLIC SURFACE via electrostatic interaction with negatively charged lipids

• myelin compaction and mediate adhesion between cytosolic surfaces of myelin sheath

Shiverer mutation I

mutation deleting majority of MBP gene leading to reduced amount of MBP, thin & loosely packed myelin sheath if even present

• symptoms are shivering, seizures, early death etc.

proteolipid protein

aka PLP

Most abundant protein in mammalian CNS & highly conserved between species.

Encoded on the X chromosome in the PLP1 gene, part of the tetraspanin protein family (4 transmembrane regions).

• highly HYDROPHOBIC

• membrane adhesion and compaction

• support axonal integrity

• NOT essential for oligodendrocyte differentiation

Pelizaeus-Merzbacher disease

PLP gene mutation in humans disrupting intracellular transport and protein trafficking leading to demyelination and oligodendrocyte death.

• demyelinating neuropathies as a result

• overexpression of gene = gain of function mutation = misfolded proteins and cell death

2,3-cyclic-nucelotide phosphodiesterase

aka CNP

highly soluble protein localized in the CYTOPLASM of NON-COMPACT MYELIN and catalyzes the phosphodiester hydrolysis of 2,3 cyclic nucleotides

• associate with oligodendrocyte cytoskeleton

• KO lose nanochannels and have axonal degeneration after normal development.

Cox10

__ gene encode essential component of the terminal complex of ETC in mitochondria

• KO fail to fully metabolize glucose & ATP is made mainly from lactate

• KO impairs maturation of oligodendrocytes, loss of respiration, functional aging of mitochondria

• NO EFFECT when myelination has already occurred

monocarboxylic acid transporters

aka MCT1 & MCT2

Transport lactate to myelinated axons

Located in internodal myelin

• KO leads to axonal degeneration due to restricted metabolites transport

• axons release K+ which triggers oligodendrocytes to start glycolysis and send lactate via ____ .

metabolic switch

A ___ occurs after oligodendrocyte maturation aka after myelination is complete so that they only release pyruvate and lactate to support axons.

blood brain barrier

The ___ aka BBB prevents cholesterol import to the CNS despite it being essential to myelin membrane growth.

• myelination delayed when cholesterol synthesis is inhibited

• astrocytes can provide cholesterol-rich lipoprotein particles to oligodendrocytes as compensation.

intrinsic

___ myelination is INDEPENDENT of neural activity

adaptive

___ myelination is modulated by neural activity and is associated with increase in MBP and fractional anisotropy (which is indicative of restricted diffusion and characteristic of myelination).

• MyRF transcription factor essential for motor skill learning and oligodendrocyte differentiation.

dynamic, environmental, fucntional

CNS myelin is highly ___, and can be modified by ___ experiences and ___ activity of axons.