Biology concepts – undulipodia, primary cilia, motile cilia, ependyma,
spaceflight, pathology, osteopenia, radiation damage, osteoblast/osteoclast,
osteocytes,
 |
|
No
one wanted the elation of the moon visit to
turn
to disaster as a moon germ spread through-
out
the world and killed every living thing. So
they
moved the astronauts from splashdown to
airstream.
What a bummer that would have
been
to go all Andromeda Strain…. although it
might
have saved us from Watergate.
|
Exposing humans to space germs would be bad, but the
problems go the other way too. Astronauts have to deal with many changes to
their body due to the reductions in sunlight, exercise, circadian rhythm, and
perhaps most of all – gravity. You’d be surprised how much microgravity (in space there is still a little gravity) can mess
with your body – and alot of it has to do with some of the smallest parts of
your cells – the primary cilia.
In fact, a 2004 study showed changes in human gene
expression during regular gravitational field changes due to sun and moon right
here on Earth. If the small changes in Earth's gravity brought about by the changing position of the Sun and Moon can have measureable effects, imagine how big a deal going into space must be. A 2008 study on Rohon-Beard cells (developmental
neurons in fish and amphibians) showed that they lost primary cilia when in microgravity. So gravity matters, and it matters in part because of what it does to primary cilia.
Life on Earth has evolved in gravity. Our bodies have come
to expect a pull to the center of the Earth and for all the air of the
atmosphere above them to be pressing down on them. These forces must have molded our
anatomy and biochemistry to some degree. So if you take us off the Earth, shouldn’t
we expect some problems?
Microgravity alters the responses of the body. Processes are
lost and balances are shifted. Problems caused by these changes can manifest in
two ways; 1) they could cause problems while in space, or 2) they could cause
problems when the astronauts return to normal gravity.
 |
|
Even
though the uniforms look Russian, this
footage
comes from the US Air Force film
archive.
They were in a C-131 doing parabolic
arcs
that would provide 15 seconds of
weightlessness.
The idea was to see if cats in
space
could land on their feet. It turns out they
can
only do it if they know which way is down.
I
think the ASPCA might have a thing or two to
say
about this.
|
Muscles and Blood
Cells
Reduced gravity means that certain parts of the body don’t
get stressed. Muscles pull against resistance; no resistance means no work for
the muscles. Think about pushing off the walls of the International Space Station (ISS) while floating
around. The necessary force is greatly reduced, so the muscle doesn’t get
worked. When muscles don’t get exercise they atrophy
(a = no, and trophy = food), like the legs of paraplegics.
A 2010 study confirmed that spaceflight has an affect on
muscle fibers. The soleus muscle of the back of the leg lost 20% of its fibers
over a 180 day mission on the ISS. Peak force was lower by 35%. The types of fibers
were different as well, switching mostly to weaker thin fibers. Exercise made a
little difference, but if the astronauts were asked to move a bed soon after landing, they’d
have to call Two Guys and a Truck.
Your heart is a muscle; the heart does less work in space
too, mostly because it can pump easier and still move the same volume of blood.
We can’t say that primary cilia aren’t involved
in these muscular and cardiovascular adaptations, we just don’t have evidence
for it yet.
In similar fashion, it’s possible that primary cilia aren’t
involved in the decreased red blood cell production during spaceflight. A 2000 study shows that blood volume is decreased in space, and this triggers lysis (popping) of the youngest red
blood cells (neocytolysis).
On the other hand, immune cell function (white blood cells) rather than number is
decreased in space. Astronauts are very prone to infections when they return to
Earth, and sometimes even in space. A 2012 study showed that a significant
percentage of astronauts manifest viral, bacterial, and fungal infections.
 |
|
The
immune synapse is mediated by the
presenting
of an antigen by one cell to activate
another
cell. Many receptors and co-receptors
are
involved, and apparently putting them all in
the
right place requires IFT proteins. The bottom
image
shows the large synapse between a
dendritic
cell (blue) and a T cell (yellow).
|
However, immune cells still express IFT proteins. We learned previously that IFT proteins mediate the building and the function of both motile and immotile cilia. A 2011 study suggests that the gap between the
immune cell that presents a foreign body (antigen presenting cell) and the
immune cell that will react to it (often a T lymphocyte), is controlled by IFT
proteins. The hypothesis is that this immune
synapse (synapse is Greek for join together) is the functional equivalent of the primary cilium for immune cells.
Primary cilia are important even when they aren’t there.
Bones
Extended spaceflight wreaks havoc on your skeleton. The
reason is that your bones need gravity to keep them growing. Yep, your bones
are always growing, ….of course they’re always breaking down too.
Bones are dynamic. Osteoblasts
(osteo = bone, and blast = germ) build new mineralized
bone, while osteoclasts (clast = breaker) consume bone. As a
result, you basically have a completely new skeleton every seven years, every
two years if you're a child. Why is this necessary? Because bones are constantly
responding to changes.
Consider weight lifting - the pulling of muscles on the
bones to which they are attached stimulates osteoblast and osteoclast activity.
Growing muscles are bigger, which means they need bigger attachments to bone.
To accommodate this growth, the bones have to remodel themselves; more bone
here, less there.
 |
|
The
left micrograph shows the difference between
osteocytes
and osteoblasts. The –cytes are in the
lacunae
while the –blasts are on the edge of the
matrix.
The right image shows a lacuna and the
canaliculi
connected to it. The osteocyte with its
primary
cilium is in the lacuna. Mechanical loading
moves
the fluid in the canaliculi and bends the cilium.
|
Gravity and other forms of mechanical loading (putting weight or pressure on the bone) affects
these osteocytes. Just walking on Earth is a source of mechanical loading on bone. The force produces a signal from the osteocytes to the osteoblasts to lay down more bone. A 2104 study has developed a model system to define how osteocytes signal
osteoblasts, but we already know some things.
Like squeezing one of those worry dolls whose eyes bug out,
mechanical stress on the lacunae brings movement of the fluid in the canaliculi
and the lacunar network. This bends the primary
cilia of the osteocytes trapped in the lacunae and triggers the signal that the bone is under a
load.
The response to loading is a release hormones and other
molecules that both stimulate osteoblast activity and call for the differentiation of bone stem cells to become osteoblasts. Osteoclasts are sill doing their job
of dissolving bone matrix, but the stimulation of osteoblasts in the loaded
area tips the balance to more bone formation in that area.
 |
|
NASA
and other space agencies try to fend off some
of
the space changes in physiology by having the
astronauts
exercise in space. It doesn’t work for
muscle,
and not much for bone. Usually it works
better
if they strap the astronauts down to simulate
some
gravity.
|
The astronauts don’t
have osteoporosis. Osteopenia and osteoprosis are two different things.
Osteopenia means less bone production, but the bone that is produced is densely
mineralized. Osteoporosis results from adequate bone formation but poor
mineralization of that bone.
Osteoporosis is caused by many other things, and can be bad – but
not as bad as space osteopenia. An astronaut can lose 10x as much bone as an
osteoporosis patient in just a six-month stay in space. You go into space as a
virile astronaut and come back as frail as your great grandmother.
Balance
We learned last week about the role of primary cilia in the
vestibular system (balance). The semicircular canals in our inner ear track
rotation in space, but the utricle
and saccule sense gravity and
acceleration in a straight line. These otlithic
organs use otoconia - little mineralized
bits on the ends of sterocilia on hair cells to detect movement and gravity.
 |
|
The
semicircular canals are for rotational changes
and
have the cupula to mediate movement. The
utricle
and saccule are for gravity responses. The
macula
of each is the region where the otoconia
mediate
the movement of the hairs in response to
changes
in their position relative to gravity.
|
Radiation
Ionizing radiation is a big problem in space. The atmosphere
and ozone layer that protect Earth life from much of the radiation that could
damage our DNA. Besides creating mutations in DNA, the radiation of space can
mess with primary cilia.
Usually solitary structures on vertebrate cells, ionizing
radiation can change primary cilia number. A 2012 study showed that after
radiation exposure, some cells had multiple primary cilia. These all came from
the same ciliary pocket, and were probably due to aberrant basal body
formation. Surely this is going to mess with any affected cell’s function,
considering how important primary cilia are for sensing the cell’s immediate
environment.
Next week, we should take a look at ourselves in the mirror. Animals may look symmetric, but it's more complicated. Do we have a head to lead our body, or did our evolution of our body give us a reason to have a head?
For
more information or classroom activities, see:
Bone
–
Space
travel and the body –
Vestibular
sense -
