Public Lecture

Exercising Our Minds:

Effects of Exercise on Brain
Structure & Function

Dr. Brian R. Christie

Division of Medical Sciences, University of Victoria
Cellular and Physiological Sciences, UBC
The Brain Research Centre, UBC

The Jack Brown and

Family Alzheimer
Research Foundation
 Changes
Time might change me, but I can’t change time....
Sir David Bowie

 How we think about the brain

 Some of the people that have shaped our
view of the brain.
 How the effects of exercise on the brain is
changing our view of it again.
We were taught the brain is like a
computer.

We’re all obsolete models!

=
 Our brains are dynamic.
Like skin and muscle, brains
change in response to their
environments
The Adult Brain Contains Neural Stem Cells

New Cells
expressing
GFP
Neurogenesis
Dendrites in
Molecular Layer

Granule Cell Layer

Mossy Fiber
Projection to CA3

Neural Stem Cells

Daughter Cells
Neurogenesis in the adult human brain!

Human Cells

Rat Cells

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

The Brain is composed of billions of
interconnected cells

Donald Hebb
1904 - 1984
CONNECTIONISM

Networks;
Cells that fire together,
wire together
Neurons
Glia Neural
Endothelial/ Stem Cells
Vasculature
The Hippocampus and Memory
 Severe Epilepsy, bilateral initiation
 1953 - Performed bilateral medial temporal
lobectomy. H.M. was 27 yrs old.
Henry Gustav Molaison
Died December 2, 2008
Spent 55 yrs in a state of
permanent amnesia

William Scoville, MD Brenda Milner, Ph.D.

Sept 1, 1953 performed -Showed working and procedural
bilateral temporal lobe memory intact.
removal -Couldn’t form new explicit
memories.
Donald Hebb showed enriched environments improved learning and
memory in rats.
Kempermann and Gage showed enriched environments increased
neurogenesis in the hippocampus.
EXPERIMENTAL DESIGN
Assessing the effects of exercise.

1 2 3
Running Wheel Water maze Electrophysiology

+
BR
DU

Normal Cage Histology

+
BR
DU
 Exercise Makes Us Smarter
RESULTS

Better Focus

Faster Learning

Improved Retention

Improved memory

van Praag et al., 1999

Exercise Also Enhances Neurogenesis

Exercise increases hippocampal neurogenesis 2-3 times!

Exercise Helps New Neurons Grow

New Adolescent Adult

Cell Cell Cell
Exercise Can Also Help Old Neurons Grow!
Do New Neurons Do Anything?

Van Praag et al., 2002

Hebb’s Postulate: Synaptic Plasticity

LTP

LTD

TIME
RESULTS Exercise enhances LTP in the DG

A Runners
Controls
B
100 50

EPSP (% Change)
EPSP (% Change)

50 25

0 0

STPS -25 WTPS

-50
-30 -15 0 15 30 45 60 -30 -15 0 15 30 45 60
Time (minutes) Time (minutes)

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

Farmer et al., 2004, Neuroscience.
Exercise increases the number of spines on neurons

02970fa2
 Brian Christie, DMS, UVIC

Exercise increases BDNF and NR2B receptor

mRNA

Farmer et al., 2004

Summary so far:

1. Exercise increases the production of new

neurons 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 memory
processes.
 Brian Christie, DMS, UVIC

Can exercise be help people with

brain injury?

YES
 Brian Christie, DMS, UVIC

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 don’t 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
 Brian Christie, DMS, UVIC
Effects of Prenatal Ethanol Exposure are virtually the
diametric opposite of those of exercise.

1. There is cell loss in the Hippocampus of offspring Dr. Joanne

following prenatal ethanol exposure. Weinberg

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

3. Animals (including humans) exposed to ethanol prenatal

exhibit impaired learning.
4. It’s harder to show electrophysiological indices of learning
and memory (LTP) in animals following PNEE.

Can exercise rescue animals from the deleterious effects of PNEE?

 Brian Christie, DMS, UVIC

 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.

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

 Brian Christie, DMS, UVIC

Gestation Day 1
Female rats become
pregnant and
begin prenatal feeding or
(ethanol, pair-fed,
or ad libitum diet). 23 days

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

22 days

Female Male
Postnatal Day 22 Offspring Offspring
Pups are weaned
and housed individually in either normal cages
or cages containing an exercise wheel The offspring
according to sex and prenatal diet. Never drink
themselves

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

 Brian Christie, DMS, UVIC

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

Reference memory
160 300 PNEE runner PF runner AL runner
PNEE
140 PF
250 AL
120

Time in seconds
200

Time in seconds
100

80 150

60
100
40
50
20

0 0
1 1 2 2 3 4 4 5 5
Trial 11 over
Trial over 5 days
days
Working memory

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

180
120
160
Timeininseconds
seconds 140
100

120
80 PNEE
PF
100
60 AL
80 PNEE runner
40
Time

AL runner
60
20
40
200
-20
0
11 22 3
3 44 55
Trial 2 over 5 days
Trial 2 over 5 days
 Brian Christie, DMS, UVIC

Normal adult animals show more LTP when they are

allowed to exercise.
Ad Libitum

80
Ad Lib Runners (n=7)
EPSP Slope (% baseline)

Ad Lib Non-runner (n=4)

60

40

20

-20
-20 -10 0 10 20 30 40 50 60
Time (minutes)
 Brian Christie, DMS, UVIC

Pair-fed animals also show more LTP when they are

allowed to exercise.

Pair-Fed

80 PF-R (n=8)
Pair-Fed-NR (n=8)
EPSP Slope (% baseline)

60

40

20

-20
-20 0 20 40 60
Time (minutes)
 Brian Christie, DMS, UVIC

PNEE animals also show more LTP when they are

allowed to exercise!
PNEE

80
PNEE-R (n=7)
PNEE-NR (n=9)
EPSP Slope (% Baseline)

60

40
.

20

-20
-20 0 20 40 60
Time (min)
 Brian Christie, DMS, UVIC

After exercising, PNEE animals do slightly better than

normal “non-exercising” animals.

Ad Libitum

80 Ad Lib Runners (n=7)

Ad Lib Non-runner (n=4)
EPSP Slope (% baseline)

60 PNEE Runners (n=7)"

PNEE Non-Runners (n=9)"

40

20

-20
-20 -10 0 10 20 30 40 50 60
Time (minutes)
 Brian Christie, DMS, UVIC

DG Proliferation
45
70
Runner
40 Nonrunner
60 Nonrunner
# of BrdU cells/section

35
50
30
40
25

20
30 24 Hr 4 weeks
15
Cell Proliferation

Neurogenesis
BrdU Injection

20
10
10
5

0
PNEE Pair-fed Ad-lib
 Brian Christie, DMS, UVIC

DG Neurogenesis
1200
VE
Con
*
1000

* *
Mean # BrdU cells/hpc

800

600

400

200

0
PNEE Pair-fed Ad-lib
 Brian Christie, DMS, UVIC

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 seem
to involve the DG.
5. Early teratogen exposure can reduce neurogenesis,
synaptic plasticity, and learning.
6. Exercise may help to alleviate these deficits.
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.
 Precautions
Exercise Precautions for Individuals with TBI
See your doctor and discuss any exercise program with him/her.

Fatigue—There 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 thinking—It can take longer to process the information, make
sure to have a clear understanding of the exercise.
Memory and initiation—Poor planning and poor goal-oriented behavior
can occur. Have a properly structured workout and review.
Medications—Understand 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 Behaviors—Impulsivity, disinhibition, indecision, and
irritability are all examples. Simply focus on the task or try redirecting
the negative behavior.
 Brian Christie, DMS, UVIC
MD

MD

MD

hon

MD

MD
PhD
The Ups and Downs of Neurogenesis

Physical Activity Inactivity

Enriched Environments Isolation
Anti-depressants Depression
Anti-Oxidant Rich Foods? Brain Irradiation
Omega-3 Fatty Acids? Alcoholism
Drug use
Mental Exercise? Stress
Social Interactions? Poor Sleep

Working for the government