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
Fig. 1.3A p. 6
Typical neuron (Nerve cell) soma, perikaryon
nerve cells have typical organelles, nucleus, rough ER, Golgi apparatus,
axon hillock, dendrites
Fig. 1.3C p. 6
terminal bouton, synapse
vesicles (small, electron lucent)
Fig. 1.4 E p. 8 Dendrites have protrusions (spines) tubulin is labeled
Fig. 1.4 F p. 8 spines, actin is labeled
shows a freshman biology view of a "typical" neuron like a spinal
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
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)
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?)
oligodendroglia (CNS) and Schwann cells (PNS) to make myelin
Fig. 1.3D p. 6 myelin
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,
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.
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
Serious cases required an iron lung.
FDR had polio.
Neuron's trophic effect on muscle is seen as muscle (not directly diseased)
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
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
Might aflict motor function, vision, or others
Hits people 20-40, with deterioration but sometimes episodic, i.e. with
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,
In 2006. graduate student Matthew Hulvey gave a presentation on MS, and
a pdf of his power point show
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.
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)
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)
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
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
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
"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.
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?
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.
What is saltatory conduction and why is it advantageous?
action potential jumps from one node of Ranvier to the next, speeds action
What specific cellular component in what specific part of the nervous system
is damaged in multiple sclerosis (MS)?
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?
"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
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
Polio causes paralysis because the virus specifically and primarily damages
what kind of 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
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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