White matter disorders
Human brain development White matter/ Myelin
In embryogenis, 3 layers (mesoderm, ectroderm, White matter (sub-cortical area) is under
endoderm) have formed, then there is a Neurulation the grey matter (cortex)
process to form neural tube. Myelin is a layer of dielectric material
Neurogenesis: During the process of Neurulation, derived mainly from lipids that form a
the inner part of the neural tubebecomes the neural sheath around neuronal axons, cable-like
progenitor cells, which divide, expand, proliferate in projections that transmit electro-chemical
a high abundance messages along the length of cells in the
Neural migration: these neural progenitor cells that brain and from brain to across the body
have been proliferating in neurogenesis, need to If myelin is damaged it obstructs the
expand to reach and form a typical sixth layer of the signal flow
brain, to do this the neural stem cells should have the Myelin-related disorders affect an
intrinsic capability to migrate estimated 3 million people around the
Synapse and circuitry: Neural cells start to mature world (incidence is growing)
and form the synaptic processes, which they can then Myelin is exclusively made in vertebrates.
form synaptic connections among them Invertebratea are able to transmit signals
Formation of neurons leads to Gliogenesis, this is by having their axons ensheathed by glial
where neural progenitor cells differentiate into cells. As a consequence, action potentials
astrocytes (subtyoe of glial cells) along invertebrate axons propagate at
Gliogensis ultimately leads to myelination, where about 1 m/s, or less
the oligodendrocytes form and make the myelin Vertebrates have adapted myelin to
From synapse to mylenation: this is post-natal, so transmit singnal conduction more
most disorders occur postnatal efficiently, as transmission of signal
-Failure of these processes can lead to brain developmental conduction is much quicker with myelin
disorders, but also neuropsychiatric disorders
Structure of CNS Myelin
How is myelin mad in
human brain?
CNS- oligodendrocytes
(primary cell that make
the myelin)
o A single
oligodendrocyt
e is able to
wrap up to 80
axonal
segments
o Highly
metabolically
active cells, that
are constantly
help in intricate
process
PNS- Schwann cells
(primary cell that
makes the myelin) PNS and CNS myelin are different
o A single swann Myelin has: Proteins 30%, Lipids 70% in both
cell is able to CNS:
only wrap one myelin proteins is mainly proteolipid protein:17% (0.2% in PNS) and
axon at a given Myelin basic protein (8%) (PNS is also 8%).
time Fatty acid synthase, band 4,1- like protein and Periaxin is not present in
CNS, but is in PNS
, What Are the Functions of the Myelin? Myelogenic cycles in the
Action potential propagation/ It helps conduct signal at much higher human brain
speed Myelination starts in
Protects axons against any type of attack central and then
Metabolic support for axons to function efficiently: There is theories, as precedes to periphery
to whether oligodendrocytes is able to que metabolic support. Myelin is PNS if first to be
such a tight structure, so not much can go through it. The oligodendrocyte myelinated, then
takes up glucose through the bloodstream, the glucose generates pyruvate spinal cord then brain
and lactate to synthesise ATP through glycolysis. The lactate settles into Myelination process
the axonal segments through monocarboxylate transporter 1 and it has starts pre-Nataly, but
been shown that if you delete the MCT1, in oligodendrocyte, there is a can continue post-
defect in the myelination, supporting this theory nataly and into
Because of this transporter, the lactate and the pyruvate get into the axon adulthood
and through which allows the ATP form Myelination can also
Glutamates is formed ultimately and this activated the NMDA receptor, have a process of re-
and inducing the necessary conformational changes that trigger opening modelling, if there is
of the ion channel pore, a process referred to as gating, and glucose can any damage
come in
Visualization of myelination Cellular sequences of CNS myelin
Paul Flechsig proposed fundamental law of myelogenesis formation
Silver staining can be used to show area of myelination The oligodendrocytes are the primary
in a study this showed that pre-natally at 36 weeks there is cells for mylenation in CNS
mylenation only at brain stem, at post natal at 4/2 months To reach the mylenation stage, we
there is hardly any mylenation, one of the reasons the start from neural stem cells, which
human baby cannot walk ect later on when the baby differentiate to oligodendrocyte
can walk/talk ect. Myelination is much more developed, progenitor cells (OPC)
giving evidence that myelination is very important for 5% of cells in human brain is OPC
higher order of executive function and that the region that OPC have ability to form
is needed at the developmental stage is myelinated as we Oligodendrocytes and astrocytes and
advance sometimes a particular type of neuron
But with smaller organisms, e.g mice are able to walk Oligodendrocytes can be divided into
from birth, mice myelination is more developed a this four classical subtypes based on the
stage than mice expression of the markers they
Flechsig proposed that tracts become myelinated as they express at the developmental stage,
become functional, thereby determining the sequence of e.g OPC predominantly express pdgf
myelination alpha and when it goes into the
developmental phase , it starts to
Myelin plasticity and aging contact the axon, this is called axon
Mylenation process is not a stagnant process, but is glial contact, causing differentiation
constanly remodelling into pre myelinated oligodendrocytes
Synaptic plasticity is important in memory Only 20% of the pre myelinated
Myelin plasticity experiment mice were used and the oligodendrocytes will become mature
later stage transcription factor, which is important ot help oligodendrocytes
the cell become mature, was deleted. The mice were then During the stage of pre mylenating,
given the task to learn how to rotate on a wheel. The they express a marker called O4 and
mylenation pattern was then looked at and the mice with at the last stage of differentiation
the deleted ltranscription factor was not able to perform mature markers, such as MBP PLP1
the task, in comparison to the Wild type control. is expressed, which distinguishes
However, when the mylenation level was restored, they which subset of the oligodendrocytes
were able to perform the task thus myelin remodelling they develop into
is important to make more myelin and increase the
amount of myelin in the brain
Similarly it has been found that as new skills are bing
learned, more cortical myelin is being formed, meaning as
we learn, myelination increases
Myelination decreases and changes in structure as we
age why we see age related cognitive decline dk why
Human brain development White matter/ Myelin
In embryogenis, 3 layers (mesoderm, ectroderm, White matter (sub-cortical area) is under
endoderm) have formed, then there is a Neurulation the grey matter (cortex)
process to form neural tube. Myelin is a layer of dielectric material
Neurogenesis: During the process of Neurulation, derived mainly from lipids that form a
the inner part of the neural tubebecomes the neural sheath around neuronal axons, cable-like
progenitor cells, which divide, expand, proliferate in projections that transmit electro-chemical
a high abundance messages along the length of cells in the
Neural migration: these neural progenitor cells that brain and from brain to across the body
have been proliferating in neurogenesis, need to If myelin is damaged it obstructs the
expand to reach and form a typical sixth layer of the signal flow
brain, to do this the neural stem cells should have the Myelin-related disorders affect an
intrinsic capability to migrate estimated 3 million people around the
Synapse and circuitry: Neural cells start to mature world (incidence is growing)
and form the synaptic processes, which they can then Myelin is exclusively made in vertebrates.
form synaptic connections among them Invertebratea are able to transmit signals
Formation of neurons leads to Gliogenesis, this is by having their axons ensheathed by glial
where neural progenitor cells differentiate into cells. As a consequence, action potentials
astrocytes (subtyoe of glial cells) along invertebrate axons propagate at
Gliogensis ultimately leads to myelination, where about 1 m/s, or less
the oligodendrocytes form and make the myelin Vertebrates have adapted myelin to
From synapse to mylenation: this is post-natal, so transmit singnal conduction more
most disorders occur postnatal efficiently, as transmission of signal
-Failure of these processes can lead to brain developmental conduction is much quicker with myelin
disorders, but also neuropsychiatric disorders
Structure of CNS Myelin
How is myelin mad in
human brain?
CNS- oligodendrocytes
(primary cell that make
the myelin)
o A single
oligodendrocyt
e is able to
wrap up to 80
axonal
segments
o Highly
metabolically
active cells, that
are constantly
help in intricate
process
PNS- Schwann cells
(primary cell that
makes the myelin) PNS and CNS myelin are different
o A single swann Myelin has: Proteins 30%, Lipids 70% in both
cell is able to CNS:
only wrap one myelin proteins is mainly proteolipid protein:17% (0.2% in PNS) and
axon at a given Myelin basic protein (8%) (PNS is also 8%).
time Fatty acid synthase, band 4,1- like protein and Periaxin is not present in
CNS, but is in PNS
, What Are the Functions of the Myelin? Myelogenic cycles in the
Action potential propagation/ It helps conduct signal at much higher human brain
speed Myelination starts in
Protects axons against any type of attack central and then
Metabolic support for axons to function efficiently: There is theories, as precedes to periphery
to whether oligodendrocytes is able to que metabolic support. Myelin is PNS if first to be
such a tight structure, so not much can go through it. The oligodendrocyte myelinated, then
takes up glucose through the bloodstream, the glucose generates pyruvate spinal cord then brain
and lactate to synthesise ATP through glycolysis. The lactate settles into Myelination process
the axonal segments through monocarboxylate transporter 1 and it has starts pre-Nataly, but
been shown that if you delete the MCT1, in oligodendrocyte, there is a can continue post-
defect in the myelination, supporting this theory nataly and into
Because of this transporter, the lactate and the pyruvate get into the axon adulthood
and through which allows the ATP form Myelination can also
Glutamates is formed ultimately and this activated the NMDA receptor, have a process of re-
and inducing the necessary conformational changes that trigger opening modelling, if there is
of the ion channel pore, a process referred to as gating, and glucose can any damage
come in
Visualization of myelination Cellular sequences of CNS myelin
Paul Flechsig proposed fundamental law of myelogenesis formation
Silver staining can be used to show area of myelination The oligodendrocytes are the primary
in a study this showed that pre-natally at 36 weeks there is cells for mylenation in CNS
mylenation only at brain stem, at post natal at 4/2 months To reach the mylenation stage, we
there is hardly any mylenation, one of the reasons the start from neural stem cells, which
human baby cannot walk ect later on when the baby differentiate to oligodendrocyte
can walk/talk ect. Myelination is much more developed, progenitor cells (OPC)
giving evidence that myelination is very important for 5% of cells in human brain is OPC
higher order of executive function and that the region that OPC have ability to form
is needed at the developmental stage is myelinated as we Oligodendrocytes and astrocytes and
advance sometimes a particular type of neuron
But with smaller organisms, e.g mice are able to walk Oligodendrocytes can be divided into
from birth, mice myelination is more developed a this four classical subtypes based on the
stage than mice expression of the markers they
Flechsig proposed that tracts become myelinated as they express at the developmental stage,
become functional, thereby determining the sequence of e.g OPC predominantly express pdgf
myelination alpha and when it goes into the
developmental phase , it starts to
Myelin plasticity and aging contact the axon, this is called axon
Mylenation process is not a stagnant process, but is glial contact, causing differentiation
constanly remodelling into pre myelinated oligodendrocytes
Synaptic plasticity is important in memory Only 20% of the pre myelinated
Myelin plasticity experiment mice were used and the oligodendrocytes will become mature
later stage transcription factor, which is important ot help oligodendrocytes
the cell become mature, was deleted. The mice were then During the stage of pre mylenating,
given the task to learn how to rotate on a wheel. The they express a marker called O4 and
mylenation pattern was then looked at and the mice with at the last stage of differentiation
the deleted ltranscription factor was not able to perform mature markers, such as MBP PLP1
the task, in comparison to the Wild type control. is expressed, which distinguishes
However, when the mylenation level was restored, they which subset of the oligodendrocytes
were able to perform the task thus myelin remodelling they develop into
is important to make more myelin and increase the
amount of myelin in the brain
Similarly it has been found that as new skills are bing
learned, more cortical myelin is being formed, meaning as
we learn, myelination increases
Myelination decreases and changes in structure as we
age why we see age related cognitive decline dk why
