Choroidal Regulation
Understanding Fluid Shifts in the Brain
Fluid balance and regulation of body fluid production are critical aspects
of life and survival on Earth. In space, without gravity exerting its usual downward
pulling effect, the fluids of the human body shift in an unnatural, headward direction.
After awhile, humans and other mammalian species adapt to the microgravity environment
which leads to changes in the regulation and distribution of these body fluids.
Previous spaceflight experiments have indicated that production of fluid in the
brain and spinal cord, cerebrospinal fluid (CSF), might be reduced in rats exposed
to microgravity.
Above: Dr. Gabrion will study the effects of microgravity
on proteins responsible for water and ion transport in the brain and in other
tissues. The choroid plexus which produces CSF is located in the cerebral ventricles
(left). The right panel illustrates detection of aquaporin 1 messenger RNAs in
the choroid plexus (black staining). Photo credit - Gabrion
In this experiment conducted by Dr. Jacqueline Gabrion (University of Pierre
and Marie Curie, France), proteins important for CSF production, and several molecules
that regulate water and mineral transport, will be investigated in rats flown
on the Shuttle. Dr. Gabrion and her team will determine the amounts of these proteins
and molecules present in the brain in order to evaluate whether any changes have
taken place during the rats’ adaptation to microgravity. The levels of different
aquaporins (proteins that act as a channel for water transport in and out of cells)
will also be investigated in other areas of the brain and body to better understand
the regulatory responses affecting these important water channel proteins. 
Above: CSF production is influenced by the neurotransmitter
serotonin. In frozen brain sections, serotonin receptor messenger RNAs in choroid
plexus are shown in red (left). Serotonin receptors have also been detected in
choroid plexus through their capability to specifically bind a serotonin-like
probe (right, in red). Photo credit - Gabrion
In addition to producing essential and basic information about fluid production
in the brain and body, this experiment will reveal fundamental information about
the mechanisms involved in cerebral adaptation and fluid balance during spaceflight.
Background Information:
Science Spaceflight is well known to induce headward fluid shifts and thus
offers unique opportunities to analyze the role of gravity in body fluid distribution
and fluid balance. However, the difficulties involved in measuring CSF volume
and flow in these extreme experimental conditions, have prevented extensive study
of CSF production and its transport processes during adaptation to altered gravity.
To begin to understand CSF balance during adaptation to altered gravity, Dr. Gabrion
and her team initiated studies over 10 years ago to determine the effects of spaceflight
on choroidal structures and regulation in the rat.
This STS–107 experiment specifically focuses on 2 important families of
transport proteins and on the biochemical signaling molecules that regulate CSF
production. Biosynthesis of choroidal Aquaporin 1 and sodium-potassium (Na-K)
dependent ATPase will be studied using molecular staining techniques on fixed
and/or frozen samples of choroid plexus. The expression levels of different aquaporins
will also be investigated in other brain areas, the hypophysis, the kidney, and
the lung.
Above: Immunodetection of aquaporin 1 (in green) and
sodiumpotassium ATPase (in red) at the apical pole of choroid plexus, (A, B)
in a control rat and (C, D) in a ground-based model simulating some effects
of spaceflight. A net decrease in both proteins was noted at the epithelial cells,
suggesting that CSF production was decreased. Photo credit - Gabrion
This experiment is part of the Fundamental Rodent Experiments Supporting Health
(FRESH)-02 payload which consists of 13 rats housed in 3 Animal Enclosure Modules
(AEMs). The animals, which will be shared among several different investigators,
will experience microgravity for 16 days on board the Shuttle Columbia. The AEMs
have been used successfully on many previous shuttle flights.
Earth Benefits and Applications
Because of its impact on fluid balance, spaceflight provides unique opportunities
to investigate mechanisms of adaptation that involve fluid balance in the brain,
kidneys and lungs.
This experiment will contribute to a better understanding of basic mechanisms
which regulate body fluid balance and homeostasis, and is important for the advancement
of fundamental biology.
Science Discipline Supported
This experiment supports NASA’s priorities for research aimed at understanding
fundamental biological processes in which gravity is known to play a direct role
and alleviating problems that may limit astronauts’ ability to survive and/or
function during prolonged spaceflight.
Previous flight experiments have demonstrated that reduced gravity dramatically
alters the fine structure, functions, and maturation of the choroid plexus in
the rat brain. Although no direct measurements of CSF secretion in microgravity
have been performed to date, these findings indicate that adult rats likely experience
a net reduction in CSF production during spaceflight. Such results might be generalized
to humans and could partly explain headaches frequently endured by astronauts
in space.
Hardware
The Animal Enclosure Module (AEM) is a rodent habitat that provides ventilation,
continuous filtered air flow to control waste and odor, timed lighting, food in
the form of foodbars attached to the side of the cage, and a water supply which
can be refilled as required. Rodents in the cage compartment of the AEM are not
accessible but can be viewed through the clear lexan cover. This also allows for
viewing of water level remaining in the AEM water box.
The AEM has been designed for minimum crew interaction and the animals adapt
very well to this virtually selfcontained system. The only nominal operations
required are a daily hardware check, a daily visual animal health check, and periodic
water refills. Photo credit - Ames Research Center.
Principal Investigator: Dr. Jaqueline Gabrion,
University of Pierre and Marie Curie, Paris, France
Project Scientist: Marilyn Vasques,
NASA Ames Research Center
Project Manager: Rudy Aquilina,
NASA Ames Research Center
Visit Choroidal for
a printable PDF version of this research.
Visit http://spaceresearch.nasa.gov/sts-107/overview.html
to learn more about the other OBPR investigations flying on STS-107.
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