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Rationale. Voluntary wheel running. Treadmill running. BDNF. LTP. Learning & Memory. Control exercise duration, intensity, and cessation time. 1. Genetic differences 2. Effects of environment enrichment 3. Temporal relationship between the end of running and the effect of

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slide2

Rationale

Voluntary wheel running

Treadmill running

BDNF

LTP

Learning & Memory

Control exercise duration, intensity, and cessation time

1. Genetic differences

2. Effects of environment enrichment

3. Temporal relationship between the

end of running and the effect of

measurement

Stress

slide3

Background

Each of the four 5’-exons (I-IV) includes its own promotor, and is combined with the 3’ exon (V) to yield an mRNA coding for pre-pro-BDNF. The short white stretch in exon V represents an alternative splice site, giving rise to two differentially spliced mRNA variants for each of the four transcripts. Each of these mRNAs is expressed in a tissue-specific and developmentally regulated manner.

slide5

2h after

running

2d after

running

Familiarization

1 week

Treadmill exercise

4 weeks

Training

1. Citratrate synthase activity in soleus muscles

2h after

running

Confirm exercise effects

Familiarization

1 week

Acute exercise

1-3 days

severe exercise

1 days

2. Morris water maze

Spatial learning

2h after

running

Acute

severe exercise

3. ELISA

BDNF protein levels

2h after

running

4. Real-time RT-PCR

BDNF mRNA levels

5. Serum corticosterone

levels

Stress

Stress levels

Methods

slide6

Results

Acute

Stress

Groups

4-wk exercise training

Results

Sev. Exercise with familiar.

Sev. Exercise without familiar.

Immobilization plus water

Mod. Exercise

Citrate synthase activity

N.D

N.D

N.D

N.D

BDNF mRNA levels

BDNF protein levels

Escape latency

Corticosterone levels

*

slide7

Results

Acute

Stress

Groups

4-wk exercise training

Results

Sev. Exercise with familiar.

Sev. Exercise without familiar.

Immobilization plus water

Mod. Exercise

Citrate synthase activity

N.D

N.D

N.D

N.D

BDNF mRNA levels

2h; -2d

BDNF protein levels

Escape latency

Corticosterone levels

slide8

Results

Acute

Stress

Groups

4-wk exercise training

Results

Sev. Exercise with familiar.

Sev. Exercise without familiar.

Immobilization plus water

Mod. Exercise

Citrate synthase activity

N.D

N.D

N.D

N.D

BDNF mRNA levels

-d1/d3

2h; -2d



BDNF protein levels

Escape latency

Corticosterone levels

slide9

Results

Acute

Stress

Groups

4-wk exercise training

Results

Sev. Exercise with familiar.

Sev. Exercise without familiar.

Immobilization plus water

Mod. Exercise

Citrate synthase activity

N.D

N.D

N.D

N.D

BDNF mRNA levels

-d1/d3

2h; -2d

  

BDNF protein levels

Escape latency

Corticosterone levels

slide10

Results

Acute

Stress

Groups

4-wk exercise training

Results

Sev. Exercise with familiar.

Sev. Exercise without familiar.

Immobilization plus water

Mod. Exercise

Citrate synthase activity

N.D

N.D

N.D

N.D

BDNF mRNA levels

-d1/d3

2h; -2d

  

BDNF protein levels

2h; -2d

Escape latency

Corticosterone levels

slide11

Results

Acute

Stress

Groups

4-wk exercise training

Results

Sev. Exercise with familiar.

Sev. Exercise without familiar.

Immobilization plus water

Mod. Exercise

Citrate synthase activity

N.D

N.D

N.D

N.D

BDNF mRNA levels

-d1/d3

2h; -2d

  

BDNF protein levels

2h;-2d

d1/d3

Escape latency

Corticosterone levels

slide12

Results

Acute

Stress

Groups

4-wk exercise training

Results

Sev. Exercise with familiar.

Sev. Exercise without familiar.

Immobilization plus water

Mod. Exercise

Citrate synthase activity

N.D

N.D

N.D

N.D

BDNF mRNA levels

-d1/d3

2h; -2d

  

BDNF protein levels

2h;-2d

d1/d3

Escape latency

Corticosterone levels

slide13

Results

Acute

Stress

Groups

4-wk exercise training

Results

Sev. Exercise with familiar.

Sev. Exercise without familiar.

Immobilization plus water

Mod. Exercise

Citrate synthase activity

N.D

N.D

N.D

N.D

BDNF mRNA levels

-d1/d3

2h; -2d

  

BDNF protein levels

2h;-2d

d1/d3

Escape latency

Corticosterone levels

*

slide14

Results

Acute

Stress

Groups

4-wk exercise training

Results

Sev. Exercise with familiar.

Sev. Exercise without familiar.

Immobilization plus water

Mod. Exercise

Citrate synthase activity

N.D

N.D

N.D

N.D

BDNF mRNA levels

-d1/d3

2h; -2d

  

BDNF protein levels

2h;-2d

d1/d3

Escape latency

N.D

N.D

(not sig.)

N.D

Corticosterone levels

slide15

Results

Acute

Stress

Groups

4-wk exercise training

Results

Sev. Exercise with familiar.

Sev. Exercise without familiar.

Immobilization plus water

Mod. Exercise

Citrate synthase activity

N.D

N.D

N.D

N.D

BDNF mRNA levels

-d1/d3

2h; -2d

  

BDNF protein levels

2h;-2d

d1/d3

Escape latency

N.D

N.D

N.D

Corticosterone levels

-

N.D??

N.D

N.D

N.D

slide16

Conclusions

4-wk exercise training enhanced hippocampal BDNF mRNA and protein level at 2h after the last run but not after 2d.

slide17

Conclusions

4-wk exercise training enhanced hippocampal BDNF mRNA and protein level at 2h after the last run but not after 2d.

2. An acute moderate exercise increased BDNF protein levels, but not mRNA levels.

3. Under a familiarization regimen, BDNF protein and mRNA levels were increased; otherwise, they were not.

4. 4-wk exercise training promoted the spatial learning, while acute stress impaired it.

5. Exercise with a familiarization did not cause stress

slide18

Discussion

Acute

Stress

Groups

4-wk exercise training

Results

Sev. Exercise with familiar.

Sev. Exercise without familiar.

Immobilization plus water

Mod. Exercise

4-wk exercise increases BDNF protein levels to a greater extend than a single bout of exercise is due to the priming effect of repetitive exercise.

Citrate synthase activity

BDNF mRNA levels

BDNF protein levels

Escape latency

Corticosterone levels

N.D

N.D

N.D

N.D

N.D

N.D

N.D

N.D

-d1/d3

2h; -2d

  

2h;-2d

d1/d3

N.D

N.D

N.D

-

slide19

Acute

Stress

Groups

4-wk exercise training

2. Acute treadmill exercise, regardless of its intensity, may alter BDNF expression at the translational level or posttranslational level,

Results

Sev. Exercise with familiar.

Sev. Exercise without familiar.

Immobilization plus water

Mod. Exercise

Citrate synthase activity

whereas only high intensity or long-term exercise can affect gene expression at the transcriptional level.

BDNF mRNA levels

BDNF protein levels

Escape latency

Corticosterone levels

N.D

N.D

N.D

N.D

N.D

N.D

N.D

N.D

-d1/d3

2h; -2d

  

2h;-2d

d1/d3

N.D

N.D

N.D

-

Discussion

slide20

Acute

Stress

Groups

4-wk exercise training

Results

Sev. Exercise with familiar.

Sev. Exercise without familiar.

Immobilization plus water

Mod. Exercise

Citrate synthase activity

BDNF mRNA levels

BDNF protein levels

Escape latency

Corticosterone levels

N.D

N.D

N.D

N.D

N.D

N.D

N.D

N.D

-d1/d3

2h; -2d

  

2h;-2d

d1/d3

N.D

N.D

N.D

-

Discussion

3. Treadmill exercise training could improve spatial learning by elevating BDNF gene expression.