Continuing with our podcasts on nerve and the nervous system, we've talked
about neurons, we've talked about dendrites and axons, we've talked about
synapses, what I'd like to do now is talk about some of the supporting cells or
neuroglial cells in the nervous system and we can talk about the central
nervous system neuroglial cells as astrocytes, oligodendrocytes, microglial
cells and ependymal cells. Now astrocytes function to provide physical and
metabolic support for neurons. They contribute to the blood-brain barrier in
the central nervous system. We can talk about two classes of astrocytes, fibrous
astrocytes and protoplasmic astrocytes. These are actually probably different
phenotypic expressions of the same cell type, individually it's tricky to
recognize fibrous versus protoplasmic astrocytes, if you were to try to
identify the individual cells, however it is easy to pick out histologically white
matter and gray matter so we can always tell that if we've got astrocytes in
white matter, those are gonna be fibrous astrocytes whereas the protoplasmic
astrocytes are gonna always be those astrocytes within gray matter.
Oligodendrocites are a special type of glial cell that myelinate axons within
the central nervous system. The microglial cells are resident
macrophages within the central nervous system. These cells are actually derived
from monocytes and then the ependymal cells, ependymal cells line the brain
ventricles and they line the central canal of the spinal cord. Ependymal cells
are a cuboidal or a columnar shaped epithelial like cell. They primarily
absorb cerebrospinal fluid but within the choroid plexus, these ependymal cells
are modified to secrete cerebrospinal fluid. So these are the glial cells
within the central nervous system. Within the peripheral nervous system we talk
about satellite cells and schwann cells. Satellite cells
provide physical and metabolic support for the neuron cell bodies in ganglia.
Schwann cells myelinate axons in the peripheral nervous system and they
support both myelinated and unmyelinated axons and we'll show you some micro
graphs and diagrams of that in just a few minutes. This is just a cartoon to
highlight some of the glial cells within the brain so you can take this
hypothetical piece of the brain and you can look at some of the glial cells in
relation to a big neuron, so here's a neuron, here you can see some ependymal
cells like this, you can see some astrocytes like this, you can see
oligodendrocytes which are making the myelin that would wrap around the axons
in these neurons. You can see some microglial cells. Now of course there are
blood capillaries in the central nervous system, so you would expect to find cells
like pericytes and of course smooth muscle in the capillary. This cartoon
shows an oligodendrocyte, like this just indicating that a single
oligodendrocyte is wrapping myelin around multiple different axons within
the central nervous system and here the cartoon just showing a node of ranvier
and I think you appreciate a node of ranvier is a non-myelinated area within
a myelinated axon. I'll have more to say about that in just a couple of minutes.
The top panel just shows a cartoon of microglial cells and then the
histological view of microglial cells, microglial cells are not that easy to
pick up histologically but they do kind of look
like this fusiform cell, almost like a fibrous site, so if you see cells like
this little long spindle shaped cells in the central nervous system, there's a
good chance that they're microglial cells. I'm not talking about them just yet but
look at this neuron, here's a multipolar neuron, cell body like this, nucleus like
that and then ependymal cells shown on the bottom panel.
These are ependymal cells that happen to be lining
the central canal in the spinal cord and you can see the ependymal cells like
that and you can see them at the electron microscopic level and they do
put out some microvilli processes and they do put out some cilia. Here's a
protoplasmic astrocyte in gray matter and a fibrous astrocyte
in white matter, you don't have to worry that much about the staining, this is a
specialized fluorescence confocal microscope preparation to demonstrate
these are protoplasmic astrocytes. the fibers astrocytes in the white matter
are stained with antibodies the glial fibrillary acidic protein, you may have
heard of that as an important protein that forms some of these neurofibrillary
plaques in diseases like Alzheimer's. You don't need to worry about these types of
staining. You don't have to really worry about identifying protoplasmic or
fibrous astrocytes except that you would recognize them by knowing if you're in
grey or white matter. The point I want to make here is in both cases these
astrocytes notice they're putting out foot processes on to the blood vessels
and of course this is just an artist rendition but there are huge numbers of
these foot processes that essentially totally surround the blood vessels and
these give rise to the blood-brain barrier both in the gray matter and in
the white matter so the astrocytes, very important in giving rise to the
blood-brain barrier. I'm gonna jump from the central nervous system to the
peripheral nervous system because I want to talk about Schwann cells and I want
to think about myelination and here we're gonna talk about myelination on
axons in the peripheral nervous system. You should remember that Schwann cells
developed from the neural crest, it so happens they develop under the influence
of the Sox-10 genes. I don't know if you talked about that in your embryology. I'm
not gonna hold you responsible for that but it's just interesting to understand
that the Schwann cells do come from neural crest cells and they're under the
influence of Sox-10. Now the myelination process is rather interesting and
complicated to understand it in a three-dimensional manner so I'll do the
best I can with these two-dimensional images to talk about it in this podcast,
basically myelination starts as an axon lies within a groove of the Schwann cell
and as that happens, the Schwann cell becomes polarized to form two distinctly
different functional membrane domains, that's what's called an abaxonal domain
which faces the external environment and there's an adaxonal domain which is in
direct contact with the axon. Now when the Schwann cell completely encloses an
axon just by one wrapping, you form a structure that's called a mesaxon,
that's the point where the Schwann cell cytoplasms is come together as the
Schwann cell has wrapped around an axon. Now this molecule Nrg1, I'm not going
to hold you responsible for that. That's a growth factor that helps to determine
how thick a myelin sheath will be within myelinated axons. Now the tricky thing to
understand here is that myelination is created as the mesaxon wraps around the
axon in a spiraling motion and as it does that specific myelin proteins or
myelin specific proteins get expressed. Some of these myelin specific proteins
again I'm not gonna hold you responsible for the names but for example they're given
the names PO, MBP, and PMP 22. These are myelin specific proteins, we know that
mutations in the genes that code for some of these myelin specific proteins
can be very significant in causing demyelinating diseases. One thing I want
to point out and this is something that's very difficult to appreciate
histologically and even looking at electron micrographs
but you see it a lot on board exams, people talk about the major dense line
and the intra period line within a myelin sheath and this diagram is a
really good way to visualize this, imagine that as the mesaxon is wrapping
around the axon itself so the Schwann cell is wrapping around the axon, the
cytoplasm is being squeezed out between membranes of the Schwann cell, the little
bit of cytoplasm between the Schwann cell membranes contributes to what's
called the major dense line and so in the cartoon the major dense lines I just
shown is these dense black lines. The inter period line is the extracellular
space between those membranes as the membranes coil around the axon. This is
what it looks like in the early stages of myelination. Here's an unmyelinated axon
shown here and here's an axon that's early in the process of myelination. You can
see basal lamina like this, you can see basal lamina here this is the profile of
a Schwann cell and the Schwann cell would be wrapping myelin around this
axon. You can see an outer mesaxon profile like this and there at the axon
itself and then the inner mesaxon and this particular axon, it's very early in
the myelination processes maybe about six layers of myelin that are wrapped
around this. This is a very much higher power view of myelination just pick out
the major dense lines on the intra period lines and on this micrograph this
would be the axon and this would be the outer Mesaxon region of the Schwann
cell. I'm not going to ask you on an exam to highlight the intraperiod lines or
the major dense lines on the myelinated axon. The myelin sheath is segmented
because it is formed by numerous Schwann cells that are arrayed along the length
of an axon and I think you appreciate the
node of ranvier is a junction where two Schwann cells meet along an axon and at
that junction, the axon is actually devoid of myelin. The regions of the axon
that are wrapped within myelin are called the internodal segments, so here's
a node of ranvier like this, myelin sheath, another node of ranvier like this,
myelin sheath so this would be an internodal segment of the axon
another internodal segment of the axon, so here a node of ranvier, here a node of
ranvier. This is actually a bare region of the axon, no myelin just like the
initial segment of the axon has no myelin. This is very important for the
generation and conduction of the action potentials down the axon. As a Schwann
cell membrane wines around an axon, most of the Schwann cell cytoplasm is
extruded from between the opposing layers of membrane, remember that
interperiod line. Some cytoplasm does remain in what are called Schmidt-Lanterman clefts
and in perinodal cytoplasmic islands that is extremely difficult to visualize.
If you were to conceptually unroll the Schwann cell, the cytoplasm of the
Schwann cell is going to be continuous through these Schmidt-Lanterman clefts
and through this perinodal cytoplasm and let's just go to
this part of the image first. So here's an axon and here would be like if you
were envisioning unwrapping the myelin from this axon, picture that you've got a
jelly roll and you're unrolling the jelly roll
so the axon is like you know the middle of the jelly roll and so this is the
Schwann cell that's being unwrapped, this is the myelin which is shown in the
electron micrograph like this, here's this perinodal cytoplasm like this near
the nodes of ranvier so perineural cytoplasm here if that's a node,
if that's another node perinodal cytoplasm here and then the Schmidt-
Lanterman clefts would be somewhere internal to the nodes of ranvier. Here
just at a light microscopic level, you can see the axons, you can see the very
dense myelin staining with this type of a stain at the light microscopic level,
here's the node of ranvier. It's a diagrammatic view kind of a
longitudinal section so these would be the pieces of the Schwann cell forming
the myelin that's wrapping around the axon so here's the node of ranvier like
this, here would be some of the myelin sheets like this, here would be some of
the Schmidt-Lanterman clefts. So here's the deal, here's the intense myelin
sheaths, look at these membrane wrappings around this portion of the axon, notice
how there's much less membrane wrapping around the node of ranvier, much less
membrane rapping at the Schmidt- Lanterman clefts. Here again it's hard to
visualize this but here's a real histological image. I'm tracing like this
the axon see like that here's the axon, here's the myelin like this, here is a
node of ranvier so notice the myelin sheath is much narrower at this region
so this is an intranodal segment, here's another internodal segment. Now look at
these structures that look like that, they almost look like little spines on
arrow heads you can see them there, you can see some here. Those would be the
Schmidt-Lanterman clefts and you can get a little bit of a sense near the
dark arrow of something here, this would be the airy nodal region so that's kind
of to give you a sense of what the myelin wrapping would look like. Now of
course we also said that Schwann cells support unmyelinated axons, it turns out
that axons in the peripheral nervous system are going to be enveloped by
Schwann cells even if they're unmyelinated, so the cartoon here is
showing one two three four five six axons in the cartoon that are enveloped
by the Schwann cell but there's not a lot of myelin wrapping around these
axons so look at these axons, these are unmyelinated axons enveloped
by and supported by a Schwann cell, the arrows pointing out the
mesaxons of the Schwann cells. Here's a myelinated axon or a profile thereof of
a myelinated axon here, here on the edge of the micrograph would be the myelin
sheath of another myelinated axon and here you can just see some of the basal
lamina that's surrounding the entire unit of the Schwann cells with the axons.
Here just showing some neuron cell bodies and paravertebral ganglion
just to make the point that the cell bodies are surrounded by satellite cells,
remember the satellite cells are also supporting cells. These help to maintain
a controlled micro environment for the neuron cell body. At the higher
magnification, you can see the satellite cells surrounding the cell body so
here's the cell body itself, here are the satellite cells, these would
be little profiles of the axons, in the lower power micrograph you can actually
see some of the cell bodies where you can see a nucleus and a nucleolus.
Formation of the myelin sheath in the central nervous system of course occurs
by oligodendrocytes, one oligodendrocytes can wrap around many axons. The process
of myelination is similar to what occurs in the peripheral nervous system but
it's physically and mechanically more complicated I'm not going to even begin
to even attempt to describe how the myelination wraps around the axons of
the central nervous system. There are differences in myelin specific proteins
that are expressed in oligodendrocytes as opposed to the myelin specific
proteins that are expressed in Schwann cells. The differences in some of these
myelin specific proteins of the central nervous system may be involved in the
pathogenesis of some autoimmune diseases. That's something that we're not going to
talk about here, you may encounter that later in your clinical training.