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Notes for Exercise and the Brain

• Exercise and the brain something to chew
  on.(2009) van Praag H. Trends in Neuroscience.
  May, 32(5)283-90.

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• Exercise has big benefits for brain function.

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• Exercise has big benefits for brain function.
• Exercise is very good for how the brain works.

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Note-taking

• We will look at how exercise effects some things
  in the brain.
• Exercise can effect behavior (??), structure
  (??), functions (??), and biochemistry (?? ?? )
  of the brain.
• As we go through these slides, take notes. (???
  ??)

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Note-taking (??)

• We will look at how exercise effects some things
  in the brain.
• Exercise has the following effects on brain
  behavior .
• Exercise has the following effects on brain
  structure .
• Exercise has the following effects on brain
  functions .
• Exercise has the following effects on brain
  biochemistry .

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• Exercise
• improves learning and memory in humans and
  animals.
• might prevent or delay loss of cognitive (???)
  function with aging or neurodegenerative (? ???)
  disease.
• Protects against brain damage caused by stroke
  (???),
• helps recovery (??) after injury and
• is an antidepressant (????).

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Cognition is

• The process of knowing and, more precisely, the
  process of being aware, knowing, thinking,
  learning and judging.
• ??? ??(??) ??(??)??, ?? ??(??)?? ?? ? ? ??.

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Exercise and cognition in young humans

• There is a positive correlation between physical
  activity and learning and intelligence scores in
  children.
• Reaction time and vocabulary learning were faster
  immediately after intense running or after 12
  weeks of aerobic training.
• There does not seem to be a maximum effect of
  exercise in young people.
• Being active makes a functional difference.

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• Aerobic exercise in childhood might increase the
  resilience (?? ???) of the brain later in life,
  resulting in a cognitive reserve.
• A positive correlation between physical activity
  at young ages and information processing speed in
  older men (6285) was reported.

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Exercise and cognition in older humans

• In aging humans the cortex and hippocampus
  atrophy (??) and memory function declines.
• Might be attenuated (?? ??) by exercise.
• Physically fit (??) older people performed better
  on reasoning, working memory, vocabulary and
  reaction time.

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• Adults between the ages of 60 and 85 years
  exercise several times per week for several
  months to several years.
• Cognition and fitness is tested before and after
  the exercise.
• Exercise improves cognitive function.

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• Improved cognitive function is shown in
  neurophysiological measures
• electroencephalogram,
• event related potential (ERP) and
• functional magnetic resonance imaging (MRI).

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• Eg, ERP latency is decreased and amplitude is
  increased in aerobically fit people ? improved
  neuronal conduction and cortical activation.
• MRI - prefrontal and temporal gray matter volume
  was increased in active elderly people.

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electroencephalogram
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• ?? ?? ??, ?? ?? ??(event-related potential, ERP)?
  ??? ??? ??? ?? ??? ??? ???? ???? ????. ??? ????
  ?? ??? ? ??.

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ERP
FMRI
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• Mild cognitive impairment is when memory or other
  cognitive function is below normal but does not
  reduce daily functioning. It is a middle state
  between normal forgetfulness and dementia (??).

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• There are extrinsic (???) and intrinsic (???)
  sources (??) of variance (???) within the human
  population.

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• Example Alzheimers Disease (??????)
  (AD)-related genes.
• - Apoliprotein (ApoE)-e4 allele carriers
  (intrinsic)
• ? increased risk for AD.
• ? benefit more from maintaining an active
  lifestyle than non-carriers.

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• ? older ApoE-e4-positive women - aerobic fitness
  (extrinsic) positively correlated with better
  auditory, visual and spatial learning tasks.
• ? a positive correlation between exercise,
  temporal cortex activation during a learning task
  and cognition.
• ? exercise in ApoE-e4 carriers attenuated
  symptoms of memory decline.

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• 8, 9, 10, 11, 44, 45, 46, and 47 are all
  in the prefrontal region.

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Young and aged rodents (rats and mice)

• Many exercise and cognition studies of adult
  rodents.
• strongly supports the benefit of exercise for
  brain function
• insight into the underlying cellular mechanisms.

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Young and aged rodents

• Both voluntary and forced exercise enhanced
  spatial memory in maze tests.

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Young and aged rodents

• Running improved performance in
  hippocampus-dependent tasks that require limited
  movement, such as
• contextual fear conditioning,
• passive avoidance learning and
• novel object recognition.

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Young and aged rodents

• Voluntary and forced exercise ? benefits
  non-hippocampal dependent, anxiety related
  behavior, such as performance in the elevated
  plus maze.

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EPM
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• The ability to learn new tasks decreases with age
  in rodents.
• - cellular level, the number of synaptic
  contacts, synaptic strength and plasticity
  reduced in the hippocampus and cortex.

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• Physical activity benefits spatial memory in old
  rodents.
• Aged male mice with a running wheel for one month
  
• ? improved acquisition and retention of the water
  maze task.
• Treadmill training (15 min per day for 7 weeks)
• ? improved learning in the Morris water maze in
  aged rats.

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Transgenic mouse models for AD.

• ? long-term exercise started 5 months before
  disease onset improved water maze learning.
• running ? reduced the load of ß-amyloid plaques
  in both hippocampus and cortex.
• short-term running (3 weeks), started after the
  disease ? improved both working and reference
  memory in aged AD mutant mice.

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• Mechanisms that mediate the effects of exercise
  and nutrition on the brain

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• Exercise research focused on changes in
  neurotransmitters, neurotrophins and vasculature.
  
• Hippocampus, a brain area important for learning
  and memory,
• good increase in new neurons with exercise.
• Effects of running ? enhanced hippocampal
  neurogenesis.

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• Nutrition research concentrated on the
  antioxidant and neuroprotective aspects of
  various dietary supplements.
• Also, diet might exert direct effects on neuronal
  signaling.
• The effects of diet and exercise could be
  additive and/or synergistic through activation of
  common intracellular pathways (Figure 1).

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• Exercise enhances synaptic plasticity and
  learning. (a) Exercise and probably diet enhance
  neurotransmitter and trophic factor levels. These
  factors directly enhance the function of mature
  neurons and stimulate the production of new
  neurons in the hippocampus.

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Neurogenesis

• The adult mammalian brain produces new neurons in
  the olfactory bulb and dentate gyrus of the
  hippocampus throughout life.

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• The dentate gyrus is thought to contribute to the
  formation of memories and to play a role in
  depression.

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• Many extrinsic and intrinsic (epi)genetic factors
  can regulate the production of new neurons.
• affects learning and memory.
• removal of the new cells results in spatial
  memory deficits.
• the new cells are preferentially activated during
  learning tasks.
• increase in neurogenesis is associated with
  improved cognition.

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• The strongest neurogenic stimulus is exercise.
• Wheel running in rodents 34-fold or greater
  increase in the production and survival of new
  neurons in the dentate gyrus.
• effect of running on cell genesis is rapid.
• cell genesis peaks at three days.
• after 32 days of running the effect has returned
  to baseline.
• the number of immature neurons continues to
  increase at this time-point.

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• The effect of exercise on neurogenesis maintained
  throughout life in rodents.

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Synaptic plasticity

• Synaptic plasticity is the ability of the
  synapse between two neurons to change in
  strength. Mechanisms include changes in the
  quantity of neurotransmitters released into a
  synapse and changes in how effectively cells
  respond to those neurotransmitters.

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Synaptic plasticity

• We think memories are represented by
  interconnected networks of synapses in the brain,
  synaptic plasticity is one of the important
  neurochemical foundations of learning and memory.
  - wikipedia

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• Improvements in synaptic plasticity in rodents
  that run.
• Long-term potentiation (LTP) increased in
  hippocampal dentate gyrus.
• - specific for the dentate gyrus, indicating that
  neurogenesis might be important.
• - individual new neurons have a transient
  increase in LTP amplitude and a decreased
  induction threshold.
• - maybe increased expression of
  N-methyl-D-aspartic acid (NMDA) NR2B receptors in
  new neurons.

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• An exercise-induced 34-fold increase in highly
  plastic cells in the dentate gyrus might explain,
  in part, the profound effect of physical activity
  on memory function

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• Exercise affects the properties of dendritic
  spines, which are actin-rich protusions on the
  dendrites that contain excitatory synapses.

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• A dendritic spine is a small protrusion from a
  neuron's dendrite.
• Dendritic spines act as a storage site for
  synaptic strength and help transmit electrical
  signals to the neuron's cell body.
• Most spines have a head (the spine head), and a
  thin neck that connects the head of the spine to
  the dendrite.
• The dendrites of a single neuron can contain from
  thousands up to a few hundred thousand spines.
• - wikipedia

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• Changes in spine size and quantity are associated
  with LTP induction and are considered to support
  changes in synaptic strength.
• - running enhanced spine density in the dentate
  gyrus, other areas of the brain .
• - Physical activity speeds the development of
  dendritic spines in new neurons.

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Angiogenesis and vascular growth factors

• Physical activity increases production of brain
  cells and angiogenesis (??????) throughout the
  brain.
• Growth factors are important in angiogenesis and
  neurogenesis, including hippocampal neurogenesis.
  
• Running increases hippocampal growth factor gene
  expression and serum levels of growth factors.
• Blockade of growth factors slowed the increase in
  neurogenesis observed with running.

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???? vascularization

• ?? ??? ??? ?????? ???????? ???? ? ?? ? ?? ??? ??
  ???? ???? ?? ???, ??? ????????????? ???? ??? ????
  ??? ?????????? ?? ???? ?? ????, ????? ??????? ??.
  ????? ?????????? ?? ?????? ??, ??????? ??? ??, ??
  ??? ??? ????. ?? ????? ??? ?? ??, ??? ??? ????
  ??? ?? ?????, ?? ?????? ???? ? ???? ??? ?? ??
  ????? ??? ??.

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• Physical activity also activates the monoamine
  system and promotes recovery from depression.
• Antidepressant effect of exercise in humans has
  been shown to be just as strong as that of
  medications which increase serotonin.

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Cell Scaffold
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Neural Network
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• Before birth you created 15 million neurons per
  hour.
• At birth your 100 billion neurons were ready to
  organize themselves in response to your new
  environment no matter the culture, climate,
  language, or lifestyle.
• During infancy, billions of these cells joineded
  into the big networks that created your nervous
  system.
• By four or five years old, your basic cerebral
  architecture was complete.  
• But, at any age you can continue to build your
  brain and expand your mind.

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• Throughout life, your neural networks reorganize
  and reinforce themselves in response to new
  stimuli and learning experiences. This body-mind
  interaction is what stimulates brain cells to
  grow and connect with each other in complex ways.
  They do so by extending branches of intricate
  nerve fibers called dendrites. These are how
  neurons receive communication from each other. 

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• A healthy, well-functioning neuron can be
  directly linked to tens of thousands of other
  neurons, creating a total of more than a hundred
  trillion connections each capable of performing
  200 calculations per second.
• This is the structural basis of your brain's
  memory capacity and thinking ability.