PCIBC 2010 Brian Christie - Exercising Our Minds

8/7/2019 PCIBC 2010 Brian Christie - Exercising Our Minds

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Changes

How we think about the brain

Some of the people that have shaped ourview of the brain.

How the effects of exercise on the brain is

changing our view of it again.

Time might change me, but I cant change time....

Sir David Bowie


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We were taught the brain is like a

computer.

=

Were all obsolete models!


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Our brains are dynamic.

Like skin and muscle, brainschange in response to their

environments


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The Adult Brain Contains Neural Stem Cells

New Cells

expressing

GFP


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Granule Cell LayerMossy FiberProjection to CA3

Dendrites inMolecular Layer

Neural Stem CellsDaughter Cells

Neurogenesis


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Neurogenesis in the adult human brain!

Rat Cells

Eriksson et al. 1998 Nat. Med 4(11):1313

Human Cells


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The Brain is composed of billions of

interconnected cells

NeuronsGlia

Endothelial/

Vasculature

Neural

Stem Cells

Networks;

Cells that fire together,

wire together

Donald Hebb

1904 - 1984

CONNECTIONISM


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The Hippocampus and Memory Severe Epilepsy, bilateral initiation

1953 - Performed bilateral medial temporallobectomy. H.M. was 27 yrs old.

William Scoville, MD

Sept 1, 1953 performed

bilateral temporal loberemoval

Brenda Milner, Ph.D.

-Showed working and procedural

memory intact.-Couldnt form new explicit

memories.

Henry Gustav Molaison

Died December 2, 2008

Spent 55 yrs in a state ofpermanent amnesia


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Donald Hebb showed enriched environments improved learning andmemory in rats.

Kempermann and Gage showed enriched environments increased

neurogenesis in the hippocampus.


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Assessing the effects of exercise.

1

Normal Cage

Running Wheel

+

+BRDU

BRDU

2Water maze

3Electrophysiology

Histology

EXPER

IMENTALDE

SIGN


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Exercise Makes Us Smarter

van Praag et al., 1999

R

ESULT

S

Better Focus

Faster Learning

Improved Retention

Improved memory


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Exercise Also Enhances Neurogenesis

Exercise increases hippocampal neurogenesis 2-3 times!


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Exercise Helps New Neurons Grow

New

Cell

Adolescent

Cell

Adult

Cell


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Exercise Can Also Help Old Neurons Grow!


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Do New Neurons Do Anything?

Van Praag et al., 2002


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Hebbs Postulate: Synaptic Plasticity

LTP

LTD

TIME


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Exercise enhances LTP in the DG

A RunnersControls

STPS-50

0

50

100

-30 -15 0 15 30 45 60Time (minutes)

EPSP(%Cha

nge)

B

WTPS-25

0

25

50

-30 -15 0 15 30 45 60

Time (minutes)

EPSP(%Change)

van Praag et al. 1999, PNAS. 96(23):13427-31.Farmer et al., 2004, Neuroscience.

R

ESULT

S


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Exercise increases the number of spines on neurons

02970fa2

Bri Chri ti DMS UVIC


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Exercise increases BDNF and NR2B receptormRNA

Farmer et al., 2004

Brian Christie, DMS, UVIC


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Summary so far:

1. Exercise increases the production of newneurons in the brain.

2.Exercise enhances the growth of existing

dendrites on neurons.

3.Exercise enhances the number of spines on

neurons.

4.Exercise enhances synaptic plasticity

5.Exercise enhances learning and memoryprocesses.

Brian Christie DMS UVIC


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Can exercise be help people with

brain injury?


YES



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Fetal Alcohol Syndrome

Fetal Alcohol Syndrome (FAS) or Fetal Alcohol Spectrum Disorder (FASD) is caused by

women drinking alcohol while pregnant.

FAS generally refers to the spectrum of morphological and cognitive disorders that are

apparent in the offspring of heavy drinkers.

Many women dont even know they are pregnant for months after conception and

continue to drink until they find out they are pregnant. Their children are probably more

at risk for FASD than FAS.

No amount of alcohol in pregnancy has been established as safe for the fetus.

About 1% of North Americans suffer from FAS (Fetal Alcohol Syndrome) or FASD




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Effects of Prenatal Ethanol Exposure are virtually thediametric opposite of those of exercise.

1. There is cell loss in the Hippocampus of offspring

following prenatal ethanol exposure.

2. Hippocampal cells do not appear to be fully mature.

3. Animals (including humans) exposed to ethanol prenatal

exhibit impaired learning.

4. Its harder to show electrophysiological indices of learning

and memory (LTP) in animals following PNEE.

Can exercise rescue animals from the deleterious effects of PNEE?


Dr. Joanne

Weinberg



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These experiments require 3 groups of animals

1. Ad Libitum Controls (AL) 2. PNEE (35.5% ethanol derived calories)

3. Pair-fed (PF) get the same number of calories as

PNEE animals but have maltose-dextrin substituted

for ethanol.

Ad Libitum (no diet, no alcohol)Pair-fed, No EthanolEthanol Diet




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or

Gestation Day 1Female rats becomepregnant and

begin prenatal feeding(ethanol, pair-fed,or ad libitum diet).

Postnatal Day 1Special diets end.Pups are born.Litters are culled to 10(5 m and 5 f).

23 days

22 days

Female

Offspring

Male

OffspringPostnatal Day 22

Pups are weanedand housed individually in either normal cagesor cages containing an exercise wheelaccording to sex and prenatal diet.

The offspring

Never drink

themselves


* Note this is the equivalent of drinking in G1 and G2 only.



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0

50

100

150

200

250

300

1 2 3 4 5

Trial 1 over 5 days

Timeinseconds

PNEE

PF

AL

0

20

40

60

80

100

120

140

160

1 2 3 4 5

Trial 1 over 5 days

Timeinseconds

PNEE runner PF runner AL runner

0

20

40

60

80

100

120

140

160

180

1 2 3 4 5

Trial 2 over 5 days

Timeinseconds

PNEE (n=11) PF (n=13) AL (n=10)

-20

0

20

40

60

80

100

120

140

1 2 3 4 5

Trial 2 over 5 days

Timeinseconds PNEE

PF

AL

PNEE runner

AL runner

Behavioural Testing in the offspring when they are adults (P50-60).

Reference memory

Working memory




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Normal adult animals show more LTP when they areallowed to exercise.

Ad Libitum

-20

0

20

40

60

80

-20 -10 0 10 20 30 40 50 60

Time (minutes)

EPSPSlope(%

baseline

Ad Lib Runners (n=7)

Ad Lib Non-runner (n=4)




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Pair-Fed

-20

0

20

40

60

80

-20 0 20 40 60

Time (minutes)

EPSPSlope(%baselin

e)

PF-R (n=8)

Pair-Fed-NR (n=8)

Pair-fed animals also show more LTP when they areallowed to exercise.




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PNEE

-20

0

20

40

60

80

-20 0 20 40 60

Time (min)

EPSPSlope(%Bas

eline)

PNEE-R (n=7)

PNEE-NR (n=9)

.

PNEE animals also show more LTP when they areallowed to exercise!



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0

200

400

600

800

1000

1200

PNEE Pair-fed Ad-lib

Mea

n#BrdUcells/hp

c

VE

Con

*

*

*

DG Neurogenesis

, ,



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Take Home Messages

1. Exercise enhances neurogenesis in the DG.

2. Exercise enhances synaptic plasticity in the DG.

3. Exercise increases dendritic complexity in the DG.

4. Exercise enhances learning in behaviors that seemto involve the DG.

5. Early teratogen exposure can reduce neurogenesis,synaptic plasticity, and learning.

6. Exercise may help to alleviate these deficits.

, ,


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Exercise and TBI

Decrease health-risking behaviors such as

smoking and depression Increase focus and ability to stay on task

Improve mood and memory

Increase blood flow to the brain Increase body awareness

Positively effect balance

Increase heart and lung efficiency.


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PrecautionsExercise Precautions for Individuals with TBI

See your doctor and discuss any exercise program with him/her.

FatigueThere can be a number of reasons for fatigue: chronic pain,

sleep disturbances, and depression. Appropriately timed activities can

help tremendously (e.g., certain times of the day, carefully timed bursts

of aerobic activity)

Slowed thinkingIt can take longer to process the information, makesure to have a clear understanding of the exercise.

Memory and initiationPoor planning and poor goal-oriented behavior

can occur. Have a properly structured workout and review.

MedicationsUnderstand the effects of the medication on your body.

Talk with your physician before starting a fitness program to make

sure that it is an appropriate plan of action for you at this time.

Emotional BehaviorsImpulsivity, disinhibition, indecision, and

irritability are all examples. Simply focus on the task or try redirecting

the negative behavior.

B i Ch i i DMS UVIC


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MD

MD

MD

MD

hon

MD

PhD


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The Ups and Downs of Neurogenesis

Physical Activity

Enriched Environments

Anti-depressants

Anti-Oxidant Rich Foods?Omega-3 Fatty Acids?

Mental Exercise?Social Interactions?

Inactivity

Isolation

Depression

Brain IrradiationAlcoholism

Drug use

StressPoor Sleep

Working for the government

Documents

PCIBC 2010 Brian Christie - Exercising Our Minds