This document discusses the relationship between brain-derived neurotrophic factor (BDNF) and physical activity. It finds that regular exercise is associated with increased levels of BDNF and protects against cognitive decline. A study is summarized that measured serum BDNF levels in humans and found higher levels were associated with greater cardio-respiratory fitness and more physical activity. BDNF is synthesized in multiple tissues and stored in platelets, and may be released into the bloodstream during exercise in a dose-dependent manner influenced by fitness levels. Increased BDNF then influences learning, memory, and neuroplasticity through binding to receptors in the brain. More research is still needed to fully understand the acute effects of exercise on BDNF release and gene transcription.

1. BDNF and PhysicalBDNF and Physical
ActivityActivity
Roger Ramsbottom, James Currie and MichaelRoger Ramsbottom, James Currie and Michael
GilderGilder
VIVIthth
European Sports Medicine Congress, Antalya,European Sports Medicine Congress, Antalya,
Turkey, 14-18Turkey, 14-18thth
October 2009October 2009
Human Integrative Physiology Research GroupHuman Integrative Physiology Research Group
School of Life Sciences Oxford Brookes UniversitySchool of Life Sciences Oxford Brookes University

2. BDNF – What is it?BDNF – What is it?
‘Brain Derived Neurotrophic Factor’

3. ISF
Periphery
Neurons
Glia
Peripheral
Tissues
BLOOD
PlateletMuscle
Blood-Brain Barrier
CNS
BDNF
movement?
CNS
Periphery

4. Role of BDNFRole of BDNF
 It is involved with learning and memory inIt is involved with learning and memory in
adult mammalsadult mammals
 It is likely to be neuroprotectiveIt is likely to be neuroprotective

5. Exercise and hippocampal BDNFExercise and hippocampal BDNF
mRNA and protein levels in ratsmRNA and protein levels in rats
Cotman, C. W. and Brechtold, N. C. (2002) Exercise: a behavioral intervention to enhance brain health
and plasticity Trends in Neurosciences 25 (6): 295-301.

6. BDNF; a physiological modulatorBDNF; a physiological modulator
between exercise and brain health?between exercise and brain health?
 It is known that exercise is neuroprotectiveIt is known that exercise is neuroprotective
- epidemiological evidence- epidemiological evidence
 Harvard Nurses Health StudyHarvard Nurses Health Study
 The Honolulu–Asia Aging StudyThe Honolulu–Asia Aging Study
 As yet no definitive physiologicalAs yet no definitive physiological
mechanism explains this link - BDNF is amechanism explains this link - BDNF is a
prime candidateprime candidate

7.  Abbott et al. (2004)Abbott et al. (2004)
Honolulu Heart ProgrammeHonolulu Heart Programme
 2257 retired males in Hawaii (Oahu) 71-93 years2257 retired males in Hawaii (Oahu) 71-93 years
 WalkingWalking << 0.4 km a day0.4 km a day
1.8x risk of dementia1.8x risk of dementia
compared to those walkingcompared to those walking >> 3.2 km a day3.2 km a day
Regular Exercise Protects AgainstRegular Exercise Protects Against
Cognitive Decline in the ElderlyCognitive Decline in the Elderly
• Weuve et al. (2004)Weuve et al. (2004)
Nurses Health Study, Harvard UniversityNurses Health Study, Harvard University
• 18 000 women aged 71-81
• Women walking for 1.5 hours a week
↑ cognitive performance
compared to those walking < 40 minutes

8. HumanHuman BDNF studiesBDNF studies

9. Cross sectional studyCross sectional study
 Serum samples were obtained from 44 healthySerum samples were obtained from 44 healthy
human volunteers.human volunteers.
 These samples were assayed for BDNF protein.These samples were assayed for BDNF protein.
 BDNF levels were then compared toBDNF levels were then compared to
participants’ cardio-respiratory fitness (estimatedparticipants’ cardio-respiratory fitness (estimated
VVOO22max) and levels of habitual physical activitymax) and levels of habitual physical activity
(via a validated questionnaire)(via a validated questionnaire)

10. Method: Estimation
of aerobic fitness
(VO2 max; L min-1
)

11. Initial hypothesisInitial hypothesis
Physical Activity
Serum
BDNF

12. Currie, J., Ramsbottom, R., Ludlow, H., Nevill, A. and Gilder, M. (2009) Cardio-respiratory fitness,
habitual physical activity and serum brain derived neurotrophic factor (BDNF) in men and women
Neuroscience Letters 451: 152-155.

13. 1
2
3
4
5
6
1 2 3 4 5 6 7 8
Baecke Sport Score
EstimatedVO2max(Lmin-1
)
r=0.536, P =0.000, n=43
20
40
60
80
100
120
1 2 3 4 5 6 7 8
Baecke Sport Score
Seatedheartrate(bmin-1
)
r=-0.438, P =0.000, n=43

14. Low volume exerciser
(Heart rate 84 b min-1
)
High volume exerciser
(Heart rate 58 b min-1
)
PoincarPoincaréé plotsplots
Gilder, M. and Ramsbottom, R. (2008) Measures of cardiac autonomic control in women with differing
volumes of physical activity Journal of Sports Sciences 26 (7): 781-786.

15. 0.200
0.400
0.600
0.800
1.000
1.200
1 2 3 4 5 6 7 8
Baecke Sport Score
Poincaredimension(SD12)
r=0.272, P =0.233, n=21

16. How can CNS BDNF levels beHow can CNS BDNF levels be
increased?increased?

17. Exercise and serum BDNF concentrationExercise and serum BDNF concentration
Study Subjects Ex.
Intensity
[BDNF]-pre [BDNF]-post
Return to
baseline
Vega (2006) athletes (n=8) aerobic (easy) 6.0 6.0-6.2 no change
exhaustive 6.0 8.6 >15 min
Gold (2003) 14W, 6M
16W, 9M (MS)
60%VO2max 4.72 6.9 >30 min
60%VO2max 4.44 6.9 >30 min
Ferris (2007) 4W, 11M VTH-20 (low) 18.5 20.0 no
measure
VTH+10 (high) 19.0 21.0 no
measure
exhaustive 17.0 no measure22.5
(W, women; M, men; MS, multiple sclerosis; VTH, ventilatory threshold; BDNF
concentration ng mL-1
; 60%VO2max - moderate)

18. Exercise and serum BDNF concentrationExercise and serum BDNF concentration
Study Subjects Ex.
Intensity
[BDNF]-pre [BDNF]-post
Return to
baseline
Winter (2007) 27M sedentary 0.98 1.01 no
measure
moderate 0.85 0.97 no
measure
Tang (2007) 8W, 8M moderate 30.9 34.5
(10 min)
35 min
Castellano
(2008)
8W, 3M 60%VO2peak 20.15 18.00 not elevated
60%VO2peak 10.05 14.00 120 min
(W, women; M, men; MS, multiple sclerosis; BDNF concentration ng mL-1
;
60%VO2peak - moderate)
intense 1.04 1.17 no
measure
8W, 3M (MS)

19. Suwa, M. et al. (2006) Serum brain-derived neurotrophic factor level is increased and associated with
obesity in newly diagnosed female patients with type 2 diabetes mellitus Metabolism Clinical and
Experimental 55: 852-857.
BDNF and energy metabolismBDNF and energy metabolism

20. BDNF and energy metabolismBDNF and energy metabolism
Suwa, M. et al. (2006) Serum brain-derived neurotrophic factor level is increased and associated with
obesity in newly diagnosed female patients with type 2 diabetes mellitus Metabolism Clinical and
Experimental 55: 852-857.

21. Start Exercise End Exercise
High fitness level
Low
fitness
level
Time (min)
Serum[BDNF]ngmL-1 Revised HypothesisRevised Hypothesis

22. The Neurotrophin FamilyThe Neurotrophin Family

23. Synthesis and StorageSynthesis and Storage
 Synthesis is via a number of tissuesSynthesis is via a number of tissues
– neuronsneurons
– skeletal muscle cellsskeletal muscle cells
– vascular endothelial cellsvascular endothelial cells
 Storage - main storage site outside of theStorage - main storage site outside of the
CNS are plateletsCNS are platelets
 Uptake and release mechanism unknownUptake and release mechanism unknown

24. Characteristics of BDNFCharacteristics of BDNF
Cotman, C. W. and Brechtold, N. C. (2002) Exercise: a behavioral intervention to enhance brain health
and plasticity Trends in Neurosciences 25 (6): 295-301.
(a) Transport to synapses
(b) BDNF binds to TrkB
- presynaptically to modify
transmitter release
- postsynaptically to modify
postsynaptic sensitivity

25. Exercise induces growth factorExercise induces growth factor
cascadescascades
Cotman, C. W., Brechtold, N. C. and Christie, L-A. (2007) Exercise builds brain health: key roles of
growth factor cascades and inflammation Trends in Neurosciences 30 (9): 464-472.

26. Currie, J., Ramsbottom, R., Ludlow, H., Nevill, A. and Gilder, M. (2009) Cardio-respiratory fitness,
habitual physical activity and serum brain derived neurotrophic factor (BDNF) in men and women
Neuroscience Letters 451: 152-155.

27. van Praag, H. (2009) Exercise and the brain: something to chew on Trends in Neurosciences 32 (5): 283-
290.

28. Currie, J., Ramsbottom, R., Ludlow, H., Nevill, A. and Gilder, M. (2009) Cardio-respiratory fitness,
habitual physical activity and serum brain derived neurotrophic factor (BDNF) in men and women
Neuroscience Letters 451: 152-155.

29. Relationship between aerobicRelationship between aerobic
fitness and autonomic functionfitness and autonomic function
1
2
3
4
5
6
0.200 0.400 0.600 0.800 1.000 1.200
Poincare dimension (SD12)
EstimatedVO2max(Lmin-1
)
r=0.462, P =0.035, n=21

30. Relationship between serum BDNFRelationship between serum BDNF
concentration and autonomic functionconcentration and autonomic function
0
2
4
6
8
10
12
14
16
18
20
0.200 0.400 0.600 0.800 1.000 1.200
Poincare dimension (SD12)
SerumBDNF(ngmL-1
)
r=-0.324, P =0.152, n=21

31. What next?What next?
 Phase II study is to examine the acute responsePhase II study is to examine the acute response
to exercise. Looking at a spectrum of active -to exercise. Looking at a spectrum of active -
sedentary participants.sedentary participants.
 Temporal profile of serum BDNF followingTemporal profile of serum BDNF following
exercise?exercise?
 Magnitude of platelet BDNF release into serumMagnitude of platelet BDNF release into serum
following exercise?following exercise?

32. Effects of exercise on geneEffects of exercise on gene
transcriptiontranscription
Cotman, C. W. and Brechtold, N. C. (2002) Exercise: a behavioral intervention to enhance brain health
and plasticity Trends in Neurosciences 25 (6): 295-301.