9/27/22

Yung-Shu Kuan, Sep. 27, 2022

The Brain Tissues

1. White ma/er :
myelinated axons (myelin sheath , ~50% mass) , glial cells and blood vessels
2. Gray ma/er :
nerve cell bodies with their extensive dendri5c arboriza5ons
(Neurons)
Frontal plane

Transverse
plane

Gray ma/er
White ma/er
Transverse secBon of spinal cord Frontal secBon of cerebrum of brain

h/p://mulBple-sclerosis-research.blogspot.com/2015/01/educaBon-whats-mri.html

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Neurons communicate with each others through synapses

Synapses can occur between a wide range of different regions of the neuron.

Node of Ranvier

Two types: Electric synapses & Chemical synapses

Func5on of myelin : to increase the speed of electrical impulses

Myelin serves to increase the speed of electrical communicaBon between neurons.

h"ps://www.brainfacts.org/

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The Myelin Sheath

A greatly extended and modified plasma membrane wrapped around

the nerve axon in a spiral fashion. On axon ≥ 1μm.
myelin axon
Schwann cell cytoplasm

Light micrograph of a 1μ Epon secBon of rabbit

peripheral nerve (anterior root), stained with outer mesaxon Schwann cell cytoplasm
toluidine blue
Electron micrograph of a single peripheral nerve
fiber from rabbit.
Myelin: H2O ~ 40%; lipid (70–85%, dry); protein (15–30%, dry).

The Myelin Sheath

A typical CNS myelinated fiber from the spinal cord of an adult dog

Higher magnificaBon

Higher magnificaBon (from 10-4)

Cytoplasmic

Exoplasmic
basal
basal
lamina
lamina

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The ultrastructural data on CNS myelin

No full ring of cytoplasm

surrounding the outside of
the sheath (differ from PNS)

The ultrastructural data on CNS myelin

Repeat distance:
CNS ≈ 107 Å
PNS ≈ 119 Å

No full ring of cytoplasm

surrounding the outside of
the sheath (differ from PNS)

Cytoplasmic Exoplasmic Cytoplasmic

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Chemical synapses transduce neuronal signals

Mol Cel Bio., Lodish et. al. 7th Ed.

Neuron generates ac5on poten5al by sequen5al opening and closing of

votage-gated Na+ and K+ channels
(a) ResBng state (cytosolic face negaBve)

Voltage change

Gated Na+
channel open
(b) Depolarized state (cytosolic face posiBve)

Gated K+
channel open

Mol Cel Bio., Lodish

et. al. 7th Ed.
later, First,
causes repolarizaBon causes depolarizaBon

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Opera5onal model of the voltage-gated Na+ channel.

Mol Cel Bio., Lodish et. al. 7th Ed.

Unidirectional conduction
of an action potential due
to transient inactivation of
voltage-gated Na+
channels

Mol Cel Bio., Lodish et. al. 7th Ed.

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Myelina5on increases the velocity of impulse conduc5on

Unmyelinated

arrows show the flow of acBon currents

Myelinated

axon Space Energy Temp. velocity

diameter

squid 500um 1500 5000 20°C 25m/sec

frog 12um 1 1 20°C 25m/sec

Myelina5on increases the velocity of impulse conduc5on

high densiBes of voltage-gated
Na+ and K+ channels

10-100m/sec

Mol Cel Bio., Lodish et. al. 7th Ed.

Schwann cells secrete gliomedin to instruct the Channel proteins are tethered to the node by
assembly of Na channel clusters at nodes of Ranvier binding to neurofascin186, NrCAM & ankyrinG

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The Node of Ranvier

glia–axon
Bght juncBons
(paranodal)

h"ps://www.brainfacts.org/brain-anatomy
-and-funcBon/anatomy/2015/myelin

A node of Ranvier from opBc nerve, triple- labeled using anBbodies against Na
channels (green), Caspr (red), and Kv1.2 K channels (blue) to define nodal,
paranodal and juxtaparanodal domains, respecBvely.

Myelin sheaths in CNS & PNS

Mol Cel Bio., Lodish et. al. 7th Ed.

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The CNS Myelin

lateral loops

The PNS Myelin

Schmidt-Lanterman clems
(Common in PNS, rare in the CNS.)

seal the myelin to the axolemma

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Structure of a myelin sheath in the CNS

EM

CNS

h/p://www.nature.com/nature/journal/v468/n7321/box/
nature09614_BX1.html

Structure of a myelin sheath in the PNS

EM tryptophan

PNS oligosaccharide

EM

Mol Cel Bio., Lodish et. al. 7th Ed.

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Composi5on of CNS Myelin and Brain

*cholesterol : phospholipid : galactolipid = 4:3:2 ~ 4:2:2.

outside

* Glycoolipid

Sphingolipid

inside
*

*SulfaBde is important for establishing the normal oligodendroglial–axon interacBons in the paranodal region,
abnormal distribuBon of Na and K channels also observed.
*Major ganglioside in CNS myelin is a monosialoganglioside (GM1), and there are very low amounts of the polysialogangliosides.
some (includes human) contain sialosyl- galactosylceramide (GM4).

The Proteins of Myelin Sheath

hPNS hCNS rPNS rCNS

Doublet (CNP1, CNP2)

alternaBve
splicing

21.5 21.5

18.5 18.5
17.2 17.0

14.0

*myelin basic protein (MBP) and proteolipid protein (PLP, Folch-Lees protein) making up 60 to 80%

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Mouse MBP isoforms

The a.a. sequences corresponding to the various mouse MBPs are encoded in a gene containing at least 11 exons.

Forma5on of the
Myelin Sheath mesaxon

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The Development of the Schwann cell lineage

The development of the Oligodendrocyte lineage

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Oligodendroglial lineage development & de novo myelina5on

J. Neurochem. (2019) 148, 447--461

Oligodendroglial lineage development and de novo myelinaBon

Oligodendroglial lineage development & de novo myelina5on

J. Neurochem. (2019) 148, 447--461

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The Control of Myelin forma5on

NRG/ErbB signaling that regulates both acBve myelinaBon and terminaBon of myelinaBon in Schwann cells.

Nrg-1:
neuregulin-1

Molecules involving in axon myelina5on

Nrg-1: neuregulin-1

BMC Neuroscience 2008 9:83

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iPSC-derived myelinoids to study myelin biology of humans

A human stem cell-derived

organoid model of widespread
& compact myelination

Recapitulated impaired
paranode formation in patient
-derived cultures

Pharmacological modulation of
oligodendrocyte morphology
& global myelin levels

Blocking synaptic vesicle

release leads to hypomyelination

Developmental Cell 56,

1346–1358 May 3, 2021

Muta5ons that affect the Myelin Sheath forma5on

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Examine The White MaXer by DTI

Diffusion tensor imaging (DTI) : based on magneBc resonance imaging (MRI),
extends the resoluBon and contrast of convenBonal MRI by acquiring a series
of images with mulBple imaging parameters.

DTI showed lower fracBonal

anisotropy and decreased white
ma/er density in the lateral
splenium of the corpus callosum
in individuals with fetal alcohol
syndrome.

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