Neurons and glia

from Purves et al., Chapter 1, Figures from Chapters 3, 6, 16, 22, Appendix

Diseases of the nervous system are significant
in the overall health care system
and in fulfilling the optimum quality of life

Examples: Boxes

Neurons

Fig. 1.3A p. 6
Typical neuron (Nerve cell) soma, perikaryon
nerve cells have typical organelles, nucleus, rough ER, Golgi apparatus, mitochondria
axon hillock, dendrites

Fig. 1.3C p. 6
terminal bouton, synapse
vesicles (small, electron lucent)
post-synaptic density

Fig. 1.4 E p. 8 Dendrites have protrusions (spines) tubulin is labeled
Fig. 1.4 F p. 8 spines, actin is labeled

TRANSPARENCY
shows a freshman biology view of a "typical" neuron like a spinal motor neuron

Fig. 16.5 p. 365 (shows how motor nerve branches to innervate all the muscle cells of one "motor unit" collateral)

Fig. 5.5 p. 83
Cytoskeleton
important and, in neurons, have unique properties
microtubules 25 nm diameter
Axon transport as fast as 400 mm/day
discovered by Paul Weiss (American) in 1940's - based on microtubules
kinesin moves toward + end of microtubule, anterograde (orthograde)
put radioactive proline in eye - use autoradiography for neuroanatomy
dynein moves toward - end, retrograde
herpes and rabies viruses ascend by retrograde transport
Slow (1 mm / day)

Glia

Fig. 1.5 ABC p. 9 astrocyte, oligodendrocyte, microglial cell
astrocytes - support, repair, grouping, regulate ions, neurotransmitters
microglia -> macrophages (Virchow noted phagocytosis in pathology)

Fig. A20 p. 741 (Appendix) Astrocyte end feet involved, along with capillary endothelium, in blood brain barrier
central nervous system is well sequestered from the immune system

Fig. 22.12 AB p. 502
Fig. 22.13 A p. 504
radial glia provide "railroad tracks" for migrating cells in development (but how did they get there?)

Myelin

oligodendroglia (CNS) and Schwann cells (PNS) to make myelin
Fig. 1.3D p. 6 myelin
also
Fig. 1.3G p. 6 node of Ranvier between adjacent patches of myelin
Fig. 1.5 B p. 9 oligodendrocyte
Fig. 1.5H p. 9 myelin is red, lots of channels at node of Ranvier green

Fig. 3.13 A,B p. 53
Myelin - cytoplasm squeezed out - multiple layers of membrane, high resistance, high capacitance
Channels at nodes of Ranvier

Here is an osmium tetroxide "stained" transmission electron micrograph of the many layers of membrane in myelin

nodes of Ranvier 1-2 micro meters (microns), Schwann cells 1 mm
"Saltatory" (leaping) conduction
oligodendrocyte myelinates several axons

Here is a classic diagram of an oligodendeocyte. Note that the cell myelinates several axons. Note also that the major dense line is where the cytoplasm was squeezed out and the minor dense line is where the outsides of the membranes fuse.

Recent reading: J. K. Huang et al., Glial membranes at the node of Ranvier prevent neurite outgrowth, Science 310, 1813-1817, 2005. A protein called OMgp (oligodendrocyte glycoprotein) is associated with a decrease in axonal sprouting after injury. This protein is not in myelin but in "oligodendrocyte-like cells" that make a wrapping around nodes of Ranvier. This understanding may be important in therapy and relates to the long standing dogma that there is no regeneration in the mammalian CNS.

Myelin diseases

Chapter 3 Box D multiple sclerosis

Polio (poliomyelitis) is a viral disease that damages myelin in peripheral nervous system causing paralysis; then the nerve cell degenerates.
Salk (1955, injected) then Sabin (eat sugar cube) vaccines in the 1950s, before that, only passive immunity from gamma globulin from people who had polio.
Serious cases required an iron lung.
FDR had polio.
Neuron's trophic effect on muscle is seen as muscle (not directly diseased) deteriorates.

It is thought that there is some recovery where motor neurons branch more (they already branch to innervate all of the muscle cells [fibers] of one motor unit) so that surviving neurons innervate muscle cells "abandoned" by lost nerve cells.
But at middle age, there is increased fatigue, pain and weakness (post-polio syndrome).
Cause: those sprouts are lost.
L.S. Halstead Post -polio syndrome, Scientific American, April 1998 42-47

Multiple sclerosis (MS) (Anette Funicello, Montell Williams, Richard Prior, "the president" in West Wing) damages myelin in the central nervous system
Might aflict motor function, vision, or others
Hits people 20-40, with deterioration but sometimes episodic, i.e. with remissions
Animal model - EAE (experimental allergic [autoimmune] encephalitis) to myelin basic protein.
Such a disorder used to happen with rabies vaccination when virus was grown in brain (before it was grown in eggs).
As you see from the box, there is lots of speculation as to the cause
Guillain-Barre syndrome peripheral myelin immune attack lose sensation and have weakness, sometimes severe, sometimes goes away, comes after illness, difficult to diagnose, controversy over whether it came after immunization for swine flu in Ford administration
Gina Kolata, Flu: The story of the great influenza pandemic of 1918 and the search for the virus that caused it, New York, Farrar Straus and Giroux, 1999.

In 2006. graduate student Matthew Hulvey gave a presentation on MS, and here is a pdf of his power point show

"Literature humanities"

Garrett Oppenheim (my uncle), The Golden Handicap: A spiritual Quest: a polio victim asks "why?" and turns his life around. Association of Research and enlightenment Press, 1993. An autobiography concentrating on what it was like to have that handicap and how people should treat someone with such a handicap.

AUTISM

Suggested readings

Nancy Shute, Desperate for an autism cure, Scientific American October 2010, 80-85. Now thought to affect 1/110 children, "No cause, no cure." Parents grope for expensive and "dubious therapies" (snake oil).

N Lang and C J McDougle. Help for the child with autism, Scientific American October 2013, pp 72-77. Since communication and eye contact are lacking, they do not learn. Identify them early and give them intensive training, and oxytocin (here called the cuddle chemical)

TV

In the television series Boston Legal, Jerry Espenson (portrayed by Christianson Clemenson) is a lawyer with Asperger syndrome and Tourette syndrome, closely related to Autism. (portrayed by Christian Clemenson)

Suggested Link

1998 finding (Andrew Wakefield) linking MMR (measles, mumpa, rubella) vaccine with autism was recently considered to be fraudulent. Also, evidence suggesting link of thimerosal (a preservative in vaccines) with autism is very debatable. Thimerosal was removed from childhood vaccines in 1999.

Charcot-Marie-Tooth (CMT) disease,

a peripheral neuropathy, see Wiki link. I plan to introduce a friend of mine, JH, who will chat briefly about his case. According to his neurologist, he has type 2A or 2D, axonal (not myelin) types. He has long had high arches and hammer toes. He has very thin calves. He was well along before he really had symptoms, not only motor loss, but also now some sensory loss, and now affecting the hands as well as the legs. CMT was in the 2013 presentation by graduate student Ian Hakkinen (PodCast).

Test questions from 2005 - 2012 that apply to this outline

Keeping in mind what I have said about techniques, what are you actually seeing when you refer to the electron density of a membrane or a synaptic vesicle?

electron dense heavy metals bound to membrane or vesicle contents

Give the name of a protein involved in axon transport.

tau kinesin, microtubular protein

In the neurons and glia lecture, we referred to two components of the blood brain barrier between the blood and the cerebrospinal fluid. Identify one of these.

capillary endothelium plus astrocyte end foor

Using a radioactive label, we can see where that radioactivity gets to in the brain. Name (or describe) that technique.

autoradiography, expose photographic film to histological brain slice

Identify a protein that would be found at or near the node of Ranvier but would not be foune (or would be found in much lesser amount) on or near the axon under the myelin.

sodium channels, OMgp=oligodendrocyte glycoprotein

Why would you expect membrane to have very high resistance?

except for channels, the hydrophobic milieu of fatty acids of the bilayer of phospholipids would not conduct ions

"Multiple sclerosis is an autoimmune disease." Answer either (1) To what protein? or (2) How can you get immune to a protein that belongs in your body?

myelin basic protein, its sequestration from immune surveillance has been compromised

"Major and minor dense lines alternate in the layers of myelin." Answer either (1) What makes up the major line? (2) What makes up the minor line? Or (3) What is meant by dense?

(1) the two intracellular membrane sides (2) the two extracellular membrane sides (3) electron dense, dark in a transmission electron microscope

Spines express actin that is visualized by microscopy. Answer either (1) Where is a spine? (2) Functionally, what kind of membrane does it have?

(1) on the dendrite (2) postsynaptic

The concept of the motor unit, all the muscle cells innervated by one spinal motor neuron, was introduced. How is that muscle unit related to Halstead's proposal on how he had some recovery after polio then the symptoms recurred later in life.

new muscle cells were recruited to units innervated by surviving neurons, but, by middle age, these new sprouts are lost

When radioactive proline (an amino acid) was put in the eye, it was incorporated into a protein, and this protein was later found in the brain. Name an axonal protein that was involved in this transport.

kinesin, tubulin

Something more than the endothelial cell is proposed to be responsible for the blood-brain-barrier that makes the cerebro-spinal-fluid a privileged compartment. What is the additional cell type?

astrocyte (glial cells)

"Thimerosal was removed from childhood vaccines in 1999." Answer either (1) What is thimerosal? Or (2) This argues against thimerosal being a cause of (what disorder?).

(1) a mercury-containing preservative (2) autism

I showed you a figure that indicated that channels mediating the action potential were concentrated in small localized areas along the axon. What are these places?

nodes of Ranvier

Explain the reason for the prefix "oligo-" in "oligodendrocyte."

they myelinate several axons

EAE (experimental allergic [autoimmune] encephalitis) is an animal model for what disorder?

ms

Guillain-Barre syndrome, rumored to be a consequence of the swine flu shots in the 1970's, does what to the patient's nervous system?

peripheral nerve myelin damage

What is kinesin used for?

axonal transport along microtubules

Why is saltatory conduction in the vertebrate even faster than conduction in giant invertebrate axons?

because action potential jumps from node to node

What do all the dense lines seen in myelin in the electron microscope signify?

many membrane layers

Why might the leg of a person who had suffered debilitating polio be spindly?

nerve has trophic effect on muscle

Membrane has high resistance and high capacitance. Why do multiple layers of membrane in myelin decrease current flow through the part of the axon ensheathed in myelin?

resistance in series adds, capacitance in series adds inversely

If injected into the eye, radioactive proline, an amino acid, gets incorporated into proteins. Radioactivity can be seen in area 17 by autoradiography. How would kinesin be involved?

kinesin is like the railroad car on microtubules that go down the axons

In addition to the endothelium, a process of what cell separates the blood from the cerebrospinal fluid.

astrocyte

What is saltatory conduction and why is it advantageous?

action potential jumps from one node of Ranvier to the next, speeds action potential

What specific cellular component in what specific part of the nervous system is damaged in multiple sclerosis (MS)?

myelin, CNS

In addition to the insulation provided by the multiple membrane layers of myelin, there is a concentration of what type of molecule at the node of Ranvier of the axon?

channels

"Postsynaptic density" - what technique and "staining" affords us the resolution to see this as a "density?"

Transmission electron microscopy where density is seek as electron density of heavy metals

Describe the nature of the connection of a spinal motor neuron to the muscle cells.

credit for any or some of the following: big synapse called neuromuscular junction, excitatory only, acetylcholine, nicotinic channel, ionotropic

What is the function of kinesin and dynein in the axon?

axonal transport (anterograde and retrograde respectively)

In addition to the endothelial cell, what separates the blood plasma from that privileged compartment, the cerebrospinal fluid (CSF)?

"foot" of astroglial cell

In salutatory conduction, the action potential jumps from one (what?) to the next (same thing)?

node of Ranvier

Membrane has high resistance and capacitance. Multiple membrane layers in myelin have high resistance to make an insulator. Current leaks through membrane capacitance. How come multiple membrane layers don't leak huge amounts of current through the capacitance?

capacitance adds reciprocally

Membrane layers fuse so tightly in myelin that electron dense lines from adjacent membrane layers fuse. How can there be two distinct fused appearances, major and minor dense lines?

major dense line where cytoplasm squeezed out, minor - outsides of the membranes fuse.

Polio causes paralysis because the virus specifically and primarily damages what kind of cell?

Schwann cell

Relate the concept of the motor unit with Halstead's theory of the cause of post-polio syndrome.
 
One spinal motor neuron innervates multiple muscle cells. Surviving ones sprout to innervate more during recovery. These sprouts are lost in post polio syndrome
 
How does the prefix "oligo" describe the function of the oligodendrocyte?
 
This cell myelinates multiple axons
 
"Myelin helps the action potential go faster." For the peripheral nervous system, answer either (1) It keeps jumping past what kind of cell? Or (2) It jumps from one (name of gap) to the next.
 
Schwann cell, node of Ranvier

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This page was last updated 12/7/13