BMS 538: Advanced Neuroscience Module 2

Where is the origin of Schwann cells that make myelin?

neural crest cells

Where are Schwann cells located?

peripheral nervous system (PNS).

What are the functional characteristics of Schwann cells?

form myelin around PNS axons, each cell myelinating one internode, and they also support unmyelinated axons

Define internode

the segment of myelin wrapped around an axon

Define a node of Ranvier

the gap between internodes that lacks myelin and contains many ion channels

Describe the purpose of satellite cells in the PNS

surround neuronal cell bodies in peripheral ganglia to give structural and metabolic support but NOT form myelin

What is the origin of oligodendrocytes?

neuroectodermal glial precursors

Where are oligodendrocytes found?

CNS

Describe the functional characteristics of oligodendrocytes

forms CNS myelin and can myelinate multiple axons or internodes simultaneously.

Describe the g-ratio

compares axon diameter to the total diameter of the myelinated fiber

What protein regulates the g-ratio?

Myelin basic protein

What forms the dark line of myelin?

fused cytoplasmic membrane surfaces

What forms the light line of myelin?

fused extracellular membrane surfaces

Is the g-ratio maintained during remyelination in MS?

no

Why is the g-ration not maintained during remyelination in MS?

Remyelinated axons in MS often have thinner myelin

What is the relationship of the organic structure of sulfatide and galactocerebroside

Sulfatide has two molecules that are structurally related and differ primarily by the addition of a sulfate group to galactocerebroside

Describe a proposed function of these two lipids in the myelin surrounding an axon

help stabilize and maintain the compact structure of the myelin sheath surrounding axons

Describe the human leukodystrophy associated with a deletion in the gene that normally codes for the enzyme, arylsulfatase A

Metachromatic leukodystrophy: results in accumulation of sulfatides and progressive demyelination.

Describe approaches to treating a person with this leukodystrophy

hematopoietic stem cell transplantation,

bone marrow transplantation, gene therapy approaches, and supportive medical management

Identify the human leukodystrophy associated with a defect in metabolism of very long chain fatty acids (VLCFs)

Adrenoleukodystrophy (ALD)

Describe two approaches to treating a person with this leukodystrophy

hematopoietic stem cell transplantation and dietary therapy with Lorenzo's Oil

Describe some characteristics of myelin associated glycoprotein (MAG), a protein uniquely expressed by oligodendrocytes in CNS myelin

found in the innermost layer of CNS myelin,

functions in maintaining axon-glial interactions and long-term axonal integrity

Describe some characteristics of CNP, a protein uniquely expressed by oligodendrocytes in CNS myelin

it is an oligodendrocyte-specific enzyme and is believed to play an important role in myelin formation and maintenance.

Describe some characteristics of proteolipid protein (PLP), a protein uniquely expressed by oligodendrocytes in CNS myelin

the major integral membrane protein of CNS myelin and is essential for maintaining myelin structure and stability

Describe the human leukodystrophy associated with the gene mutation that normally codes for proteolipid protein.

Pelizaeus-Merzbacher disease

Describe some physical and functional characteristics of myelin basic protein (MBP), a protein uniquely expressed by oligodendrocytes in CNS myelin.

is a highly basic, positively charged protein that promotes myelin compaction and serves as an important autoantigen in multiple sclerosis

Describe the animal model of multiple sclerosis, experimental allergic encephalomyelitis (EAE)

Experimental allergic encephalomyelitis (EAE) is produced by immunization with myelin antigens, resulting in T-cell-mediated CNS inflammation and demyelination.

Describe at least one proposed mechanism of action of how the drug, Copaxone (glatiramer acetate), might work to decrease sensitized T-lymphocytes from attacking CNS myelin.

acts as a decoy antigen that redirects immune responses away from myelin and promotes anti-inflammatory T-cell activity

Describe if oligodendrocytes can re-myelinate an intact axon after an episode of demyelination associated with multiple sclerosis.

yes they can remyelinate intact axons after demyelination, although the resulting myelin sheaths are often thinner than normal

Describe four proteins uniquely expressed by oligodendrocytes that might be used to positively identify a brain tumor as an oligodendroglioma

myelin-associated glycoprotein (MAG), CNP, proteolipid protein (PLP), and myelin basic protein (MBP).

Describe characteristics about proteins expressed in peripheral nervous system myelin.

P0 protein, PMP22, and peripheral myelin basic protein

They contribute to myelin compaction, structural stability, and normal nerve conduction

Identify which human peripheral demyelinating disorder is modeled in animals with experimental allergic neuritis.

Guillain-Barré syndrome

Identify the human peripheral neuropathy associated with a gene mutation in PMP-22

Charcot-Marie-Tooth disease type 1A

Identify the human peripheral neuropathy associated with a mutation in the gene coding for P0 protein

Charcot-Marie-Tooth disease type 1B

Provide a brief description of the type of astrocyte that contains less glial fibrillary acid protein (GFAP) and is principally found in gray matter

Protoplasmic astrocytes

Provide a brief description of the type of astrocyte that contains more GFAP and is principally found in white matter.

Fibrous astrocytes

Describe the cellular composition of the blood-brain barrier ("BBB") with emphasis on the relative location of end-feet of astrocytes

capillary endothelial cells joined by tight junctions, a basement membrane, and astrocytic end-feet that closely surround the outer surface of the blood vessels

Describe some normal functions of the blood-brain barrier.

protects the brain from toxins, regulates the movement of substances into and out of the CNS, and helps maintain a stable extracellular environment

Describe the process of reactive astrogliosis in the central nervous system

occurs when astrocytes become hypertrophic, proliferate, and increase GFAP expression following CNS injury, eventually forming a glial scar around the damaged tissue.

Describe at least one major function radial glial cells perform in the embryonic brain

provide structural support and guidance for migrating neurons during embryonic development of the nervous system.

Identify the three cellular elements forming the "tri-partate" synapse

presynaptic neuron, the postsynaptic neuron, and an astrocyte

Describe at least one proposed function of the astrocyte in the tri-partate synapse

regulate neurotransmitter concentrations at the synapse by removing and recycling neurotransmitters such as glutamate and GABA

Provide a description of proteins uniquely expressed by astrocytes that might be used to positively identify an astrocytoma brain tumor and/or as a biomarker for injuries to the brain

Glial fibrillary acidic protein (GFAP) and S100β are used both as markers for astrocytomas and as biomarkers

Describe the relative location of ependymal cells in the brain

line the walls of the ventricles.

Describe the relative location of ependymal cells in the spinal cord.

line the central canal.

Describe the relative location where ependymoma brain tumors are most commonly found in the central nervous system.

commonly found adjacent to the ventricular system of the brain or within the central canal of the spinal cord

Characteristics of "high-grade" brain tumors

high cellularity,

rapid growth,

increased malignancy,

greater invasiveness, and

poor survival rates

Characteristics of "low-grade" brain tumors

lower cellularity,

slower growth,

less malignancy, and

generally better patient survival rates

Describe the relative degree of aggressiveness of a glioblastoma multiforme (GBM) and a patient's prognosis compared to low-grade brain tumors

extremely aggressive, highly malignant grade IV brain tumor with a significantly worse prognosis than low-grade brain tumors and a much shorter survival time

Describe the significance of a "ring-enhancing mass" found on a CT scan of the human brain.

ndicates a high-grade brain tumor with central necrosis and disruption of the blood-brain barrier, allowing contrast material to accumulate around the lesion.

Describe which major part of the human brain develops a medulloblastoma

cerebellum

Identify the malignant cell in a medulloblastoma.

primitive neuroectodermal cell, often derived from granule cell precursors.

What is the clinical utility of a CT to image the human central nervous system

useful for rapidly detecting hemorrhage, skull fractures, trauma, hydrocephalus, and large masses.

What is the clinical utility of an MRI to image the human central nervous system

provides superior soft-tissue contrast and detailed anatomical images of the brain and spinal cord

What is the clinical utility of a PET scan to image the human central nervous system

evaluate metabolic and functional activity within the brain by measuring the uptake of radioactive tracers and are useful for studying tumors and brain function

What is the clinical utility of an angiography to image the human central nervous system

visualizes cerebral blood vessels and is useful for identifying aneurysms, vascular malformations, stenosis, and other abnormalities of cerebral circulation