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NASA Human Research Program Integrated Pathway to Mars 2015
PROTECTING NEURAL STRUCTURES AND COGNITIVE FUNCTION DURING
PROLONGED SPACE FLIGHT BY TARGETING THE BRAIN DERIVED
NEUROTROPHIC FACTOR MOLECULAR NETWORK
M. A. Schmidt1 and T. J. Goodwin2
Advanced Pattern Analysis & Countermeasures Group, Sovaris Aerospace, LLC, Research Innovation
Center, Colorado State University, Fort Collins, CO; Course Director, Clinical Genomics, Proteomics, &
Metabolomics, George Washington University School of Health Sciences;
2
Biomedical Research and Environmental Sciences Division, Disease Modeling and Tissue Analogues
Laboratory, NASA Johnson Space Center, Houston, TX
1
Brain derived neurotrophic factor
(BDNF) is the main activity-dependent
number
of
learning,
behavioral,
and
neurological disorders.
neurotrophin in the human nervous system.
BDNF is implicated in production of new
There is an extensive body of work
neurons from dentate gyrus stem cells
surrounding the BDNF molecular network,
(hippocampal
including
neurogenesis),
synapse
BDNF
gene
polymorphisms,
formation, sprouting of new axons, growth
methylated BDNF gene promoters, multiple
of new axons, sprouting of new dendrites,
gene transcripts, varied BDNF functional
and neuron survival.
proteins, and different BDNF receptors
Alterations in the amount or activity
of
BDNF
can
produce
(whose activation differentially drive the
significant
neuron
to
detrimental changes to cortical function and
BDNF
is
synaptic
human
mitochondrial biogenesis through PGC-1α,
brain. This can result in glial and neuronal
which can influence brain and muscle
dysfunction, which may contribute to a
metabolic efficiency.
transmission
in
the
neurogenesis
also
or
closely
apoptosis).
linked
to
range of clinical conditions, spanning a
1
NASA Human Research Program Integrated Pathway to Mars 2015
Figure 1 Brain Derived Neurotrophic Factor (BDNF) Molecular Network The BDNF molecular
network is characterized by variants of the genome, epigenome, transcriptome, proteome, and
metabolome. These molecular components, including receptors, transcription factors, and signaling
molecules, represent viable target opportunities against which to develop countermeasures for the space
environment. The cellular phenotype associated with the BDNF network is depicted at the far right.
(© Sovaris Aerospace, LLC)
BDNF AS A HUMAN SPACE FLIGHT
COUNTERMEASURE TARGET
nutrition, exercise, drug, and other types of
Earth-based
studies
reveal
that
BDNF is negatively impacted by many of
the conditions encountered in the space
environment, including oxidative stress,
radiation, psychological stressors, sleep
deprivation, and many others. A growing
body of work suggests that the BDNF
network is responsive to a range of diet,
influences.
This section explores the BDNF
network in the context of 1) protecting the
brain and nervous system in the space
environment, 2) optimizing neurobehavioral
performance in space, and 3) reducing the
residual effects of space flight on the
nervous system on return to Earth.
2