For quite a while, people considered the mind and body
separate. René Descartes himself proposed the idea of what
is called the Cartesian dualism, that whatever happens to
our body leaves our minds untouched. It was believed only
the mind can truly affect itself, and thus was born “I think,
therefore I am.” More recent scientific advances proved quite
the opposite. Our minds come from intricate neural
connections in our brains. Both our bodies and outside
influences affect the flow of messenger molecules in our
brains analogously to the way our livers or muscles can be
affected, to name a few. If anything, our minds could just be
an extension of our body, rather than its own separate entity.
For example, one of the best ways to improve our brain
function is through exercise. While research is still
discovering the complete effects of exercise on the brain,
many molecular and cellular mechanisms have already been
elucidated. Exercise is known to improve neural plasticity,
increase neurotransmitter efficiency, expand neuron counts,
and even prevent cognitive diseases.

   One of the most significant findings of exercise on brain
health was elucidated through neurotrophic factors. These
molecules act as growth factors for brain cells, increasing
cell growth, signaling, and neural wiring. Despite the
importance of these factors for our brain, their expression
depends on physical exercise. One of the most important
neurotrophins is brain-derived neurotrophic factor (BDNF).
This molecule can interact with synaptic development of
dendrites and axons, allowing them to form specialized
connections for specific neuron communication. In turn,
better neural communication can aid in learning (Cohen-
Cory et al., 2011). Improved learning can occur immediately
after exercise. Human subjects were able to improve
cognitive performances in learning new material after
running on a treadmill. The increase in memory is correlated
with BDNF concentration in the bloodstream that also spikes
during exercise (Winter et al., 2007). It is also shown that
consistent exercise can increase BDNF levels compared to
sedentary behavior in rats (Berchtold et al., 2005).
Conversely, blocking BDNF contributes to decreased
synaptic efficacy and decreased vesicle proteins, both
directly harming communication between neurons (Vaynman
et al., 2006).

Abstract
Exercise is seen to physically improve the health and function of the brain. This involves a variety of molecular and cellular
mechanisms, including significant increases of beneficial neurotrophic factors like BDNF. In addition, neurogenesis in the
hippocampus is also increased after exercise. Hippocampal vascular structures, like blood flow, are improved. Plasticity is also
improved. Additional molecular mechanisms can contribute to alleviate symptoms of aging and more serious neuropathic
diseases. Negative factors like inflammation and reactive oxygen species are mitigated.

Outline on Exercise and Brain Function
Andrew Zhang

Figure 1A: Axon expressing BDNF-GFP (in green)
superimposed with dendrites of second neuron, stained with

MAP2 (in red) (Kohara, 2001).

Figure 1B: Movement of BDNF-GFP in
axon (Kohara, 2001).

1



(Other hormones, like the catecholamines dopamine,
epinephrine, and norepinephrine were shown to increase
through exercise. These hormones are thought to be
associated with learning, as they increase signaling in the
brain. It is also shown that increased levels of BDNF
correlate with physical activity (Winter et al., 2007). There are
also other neurotrophins with levels that increase with
exercise. An example is IGF-1, which increases neuron
counts in the hippocampus. (Trej et al., 2001). NMDA
receptors, which are responsible for the health and function
of neurons, also increase with exercise (Farmer et al., 2004).
Other molecules include TNF-α and vascular endothelial
growth factor (VEGF). Both these molecules improve
vascular health, including blood vessel growth and
differentiation throughout the body. TNF-α can also increase
integrin protein production, which helps cells bind to
extracellular structures. These activities can directly impact
the vascular supply of nutrients in the brain (Ding et al.,
2006). Because exercise can promote neurotrophic factors
and hormones to signal in the brain, all of these effects can
lead to a much healthier brain.

   While the human brain’s overall structure remains stable
over adulthood, it can undergo slight changes for the better.
Exercise can induce these modifications to physical
structures. For example, exercise appears to promote
neurogenesis, the creation of new neurons. While in most of
the brain, the number of neurons stays the same throughout
life, the number of neurons can increase in the hippocampus.
Most of the newly generated neurons appear in the
hippocampal dentate gyrus, a region highly responsible for
learning and storing long-term memories (Cho et al., 2013).
Higher rates of cell growth appeared in these regions for rats
performing consistent treadmill exercise (Heo et al., 2014).
Brain scans in animal studies have also shown improvement
from exercise in vascular structures in the brain, like
increased blood flow and permeability of the blood brain
barrier (Yau et al., 2014). These are all correlated with
supplying nutrients and cleansing factors to grow and protect
neurons. Brain scans in mice have also confirmed greater
growth in hippocampal areas after consistent exercise.
Similarly, brain scans in humans have shown analogous
changes in the hippocampus as well. The same human
subjects were tested in cognitive trials like delayed recall,
recognition, and source memory. Higher cognitive
performance correlated significantly with more exercise
(Peirera et al., 2007). Additionally, young neurons appear to
contribute a greater learning potential. New neurons
generate faster calcium and sodium concentration spikes,
affecting action potentials and signal transduction to
neighboring neurons. These neurons also change their
behaviors more permanently to signals, compared to older
neurons. (Schmidt-Hieber et al., 2004). These neurons are
able to express greater responses to lower levels of signal as
they mature, exhibiting long term potentiation. Older neurons
are more resistant to these changes (Ge et al., 2007). Long
term potentiation indicates increased plasticity, the ability to
rewire neural circuits. Plasticity in the brain allows it to
encode new information and boosts learning. 

Therefore, as consistent exercise increases new neurons, it
ultimately leads to more plasticity to the brain and thus
increased learning.

2

Figure 2A: Heat map showing neurogenesis activity in mice, based on
cerebral blood volume (Peirera et al., 2007).

Figure 2B: Heat map showing neurogenesis activity in humans, based on
cerebral blood volume (Peirera et al., 2007).

   Exercise is associated with broader health effects as well.
Even though neurological decline is correlated with aging,
exercise has been shown to minimize and reverse these
trends. For example, for older subjects, aerobic fitness has
been associated with better performances on cognitive tasks,
as well as retaining larger hippocampal sizes in the brain
(Erickson et al., 2009). These trends also extend to
symptoms of neurodegenerative diseases that tend to
amplify in older age. For example, as exercise promotes
neurogenesis in the hippocampus, it helps combat neuron
loss in many diseases like Alzheimer’s (Yau et al., 2014).
Exercise is also seen to alleviate symptoms of diseases. In
rats exhibiting symptoms of Parkinson’s disease, consistent
exercise appears to reduce short term memory damage (Cho
et al., 2013). Similar findings are shown for rats exhibiting
Alzheimer’s symptoms, with exercise correlated with better
performance in spatial learning (Heo et al., 2014). While
exercise cannot cure neurodegenerative diseases, they can
alleviate symptoms and improve quality of life for people with
these diseases. 
In addition to preventing neurodegenerative conditions,
exercise also protects against physical damage to the brain.
For example, exercise is shown to protect against stroke-like
symptoms in the brain. In stroke, blood flow is deficient in the
brain, which can cause swelling and cell death. In animal
studies, these symptoms are reduced in animals who
performed consistent exercise (Ding et al., 2006). Other
physical damages to the brain come from reactive oxidative
species (ROS), for example. 

Brain Matters・Volume V Issue ii



 These are molecules that can originate as byproducts of
metabolic reactions. However, ROS react inappropriately with
other molecules in cells, stopping proper pathways for normal
function. This can even affect signaling and cell survival.
Exercise increases the amount of antioxidant enzymes in
cells, protecting cellular function (Radak et al., 2016). In
animal studies, the rat brain showed an increase in protease
activity in cells in response to exercise. These proteases are
responsible for breaking down proteins, including misfolded
and damaged proteins that act as ROS (Ogonovsky et al.,
2005). Exercise provides increased antioxidant protection,
which protects the overall health and function of the brain.

  Overall, exercise appears to play an overwhelmingly
positive influence on the brain. Neurotrophins increase their
function after exercise, promoting brain health and learning.
Structures of the brain responsible for learning also change.
Neurons increase their potential for efficient communication.
Exercise also alleviates aging and neurodegenerative
symptoms. Despite the knowledge already known about
exercise, there is still much more to learn about its effects on
the brain. Exercise also improves the rest of the body, in
addition to the brain. Based on current knowledge of physical
activity, consistent exercise would be a wise choice for
improving quality of life. 

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Brain Matters・Volume V Issue ii