8 - Myelination-Related Disorders

What are four main roles of myelin and oligodendrocytes?

Axonal insulation, saltatory conduction, neuronal maintenance, and regulation of axonal sprouting

What does neuronal maintenance by myelin do?

Supports neuronal survival and axonal integrity

What is regulation of axonal sprouting done by myelin?

Inhibitory factors block axonal outgrowth

When does myelination occur?

Second trimester and onward

When does the myelination process peak?

During first 2 years of postnatal life

What are the two steps of the myelination process?

Oligodendroglia proliferation/differentiation and myelin deposition around axons

What are the four stages of oligodendrocyte development?

Oligodendrocyte progenitor cells, pre-oligodendrocytes, immature oligodendrocytes and mature oligodendrocytes

What is the first stage of oligodendrocyte development?

Oligodendrocyte progenitor cells

What is the second stage of oligodendrocyte development?

Pre-oligodendrocytes

What is the third stage of oligodendrocyte development?

Immature oligodendrocytes

What is the fourth stage of oligodendrocyte development?

Mature oligodendrocytes

When is the oligodendrocyte progenitor cell stage?

Mid-gestation to early postnatal period

What controls each transition step during oligodendrocyte lineage progression?

Interplay between extrinsic and intrinsic factors

When is the pre-oligodendrocyte stage?

Before term

What oligodendrocyte stages are multipolar?

Pre-oligodendrocytes, immature and mature oligodendrocytes

What is the shape of neurons in oligodendrocyte progenitor cells?

Bipolar

What is the mitosis pattern in OPCs?

Mitotically active and migratory

What is the mitosis pattern in pre-OLs?

Mitotic

What OL development cells are post-mitotic?

Immature and mature OLs

Do all OPCs differentiate into pre-OLs?

No

When is the immature OL stage?

At term

When is the mature OL stage?

Following term

What OLs are myelinating?

Only mature OLs

What is another term for immature OLs?

Pre-myelinating OLs

What is the first possible mechanism of myelin-related disorders?

Arrested OL lineage development

What is the arrested OL lineage development mechanism?

OPCs stop differentiating which could be due to imbalance between intrinsic vs extrinsic factors or something genetic

What is the second possible mechanism of myelin-related disorders?

OL dysfunction or process loss

What is the OL dysfunction or process loss mechanism?

OPCs are differentiated but something is wrong functionally with the mature OLs

What is the third possible mechanism of myelin-related disorders?

Primary axonal injury with abnormal signalling to OL

What is the primary axonal injury with abnormal signalling to OL mechanism?

Nothing wrong with structure/function of OLs but axons are not releasing signals to OLs to be myelinated

What is prematurity?

Birth occurring before 37-week gestation

How is the third trimester important for brain growth?

Cells are migrating and differentiating and myelination begins

What happens when brain development is disrupted with prematurity?

Risk of developing complications increases

What happens to lung development and cerebral vasculature in prematurity?

Both are immature which leads to substantial hypoxic injury to the developing brain

What is the result of hypoxic and inflammatory conditions in premature babies?

Damaged white mature

What OLs are present in prematurity?

OPCs and pre-OLs

How are OPCs and pre-OLs sensitive in prematurity?

OPCs fail to differentiate and pre-OLs are susceptible to hypoxic-related cell death

What is the role of microglia with myelination under normal conditions?

Microglia release factors that facilitate myelination

What happens to microglia involved in myelination under hypoxic conditions?

Microglia release cytokines which inhibit OPCs from differentiating

What occurs as a result of reduced OL populations in preterm birth?

Cognitive dysfunction from delayed and reduced myelination

What is +OLIG2?

OL lineage marker expressed by OPCs and maturing OLs

What is +NG2?

Selective marker for OPCs

What levels of OLIG2 reactive cells are seen in schizophrenia?

Decreased density

What levels of NG2 reactive cells are seen in schizophrenia?

No changes in density

What do findings about NG2 and OLIG2 suggest?

Process of differentiation of OPCs into maturing oligodendrocytes may be affected

What is the most common nutrient deficiency?

Iron

What neurodevelopmental processes are negatively affected by iron deficiency?

Neurogenesis, development and myelination

What are effects of iron deficiency?

Affected language learning and behaviour, altered motor function and coordination

Is iron deficiency reversible?

Not fully reversible due to critical windows of vulnerability in early development

How are iron and oligodendrocytes related in normal conditions?

Iron is increased in the brain during peak myelination due to high energy demand

What are the levels of iron in white matter?

White matter stains strongly for iron

What happens to myelination when there is a decrease in iron availability?

Deficiency decreases myelin proteins, lipid and cholesterol levels and is associated with hypomyelination

What are experimental treatments used for myelination-related disorders?

Erythropoietin treatment and endogenous regeneration

What are the main treatments used for myelination related disorders?

Regular appointments with primary care provider, environmental enrichment. andearly intervention programs