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BDNF LTP Learning & Memory Voluntary wheel runningTreadmill running 1. Genetic differences 2. Effects of environment enrichment 3. Temporal relationship.

Dec 14, 2015

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Blaise Hixon
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Page 1: BDNF LTP Learning & Memory Voluntary wheel runningTreadmill running 1. Genetic differences 2. Effects of environment enrichment 3. Temporal relationship.
Page 2: BDNF LTP Learning & Memory Voluntary wheel runningTreadmill running 1. Genetic differences 2. Effects of environment enrichment 3. Temporal relationship.

BDNF

LTP

Learning & Memory

Voluntary wheel running Treadmill running

1. Genetic differences 2. Effects of environment enrichment 3. Temporal relationship between the end of running and the effect of measurement

Stress

Control exercise duration, intensity, and cessation time

Page 3: BDNF LTP Learning & Memory Voluntary wheel runningTreadmill running 1. Genetic differences 2. Effects of environment enrichment 3. Temporal relationship.

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.

Page 4: BDNF LTP Learning & Memory Voluntary wheel runningTreadmill running 1. Genetic differences 2. Effects of environment enrichment 3. Temporal relationship.

How different treadmill exercise protocols would affect rat hippocampal BDNF gene expression?

Page 5: BDNF LTP Learning & Memory Voluntary wheel runningTreadmill running 1. Genetic differences 2. Effects of environment enrichment 3. Temporal relationship.

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.

severe exercise

2h after running

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.

2h after running

Stress

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.

Familiarization 1 week

Acute exercise 1-3 days

severe exercise 1 days

2h after running

Acute

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.

Familiarization 1 week

Treadmill exercise 4 weeks

2h after running

2d after running

Training1. Citratrate synthase activity in soleus muscles

Confirm exercise effects

2. Morris water maze Spatial learning

3. ELISA BDNF protein levels

4. Real-time RT-PCR BDNF mRNA levels

5. Serum corticosterone levels Stress levels

Page 6: BDNF LTP Learning & Memory Voluntary wheel runningTreadmill running 1. Genetic differences 2. Effects of environment enrichment 3. Temporal relationship.

Citrate synthase activity

BDNF mRNA levels

BDNF protein levels

Escape latency

Corticosterone levels

4-wk exercise training Mod. Exercise

Sev. Exercise with familiar.

Sev. Exercise without familiar.

Immobilization plus water

Acute Stress

Results Groups

0

0.5

1

1.5

C E

Cit

rate

syn

thas

e ac

tivi

ty *

N.D N.D N.D N.D

Page 7: BDNF LTP Learning & Memory Voluntary wheel runningTreadmill running 1. Genetic differences 2. Effects of environment enrichment 3. Temporal relationship.

2h; -2d

Citrate synthase activity

BDNF mRNA levels

BDNF protein levels

Escape latency

Corticosterone levels

4-wk exercise training Mod. Exercise

Sev. Exercise with familiar.

Sev. Exercise without familiar.

Immobilization plus water

Acute Stress

Results Groups

N.D N.D N.D N.D

Page 8: BDNF LTP Learning & Memory Voluntary wheel runningTreadmill running 1. Genetic differences 2. Effects of environment enrichment 3. Temporal relationship.

2h; -2d

Citrate synthase activity

BDNF mRNA levels

BDNF protein levels

Escape latency

Corticosterone levels

4-wk exercise training Mod. Exercise

Sev. Exercise with familiar.

Sev. Exercise without familiar.

Immobilization plus water

Acute Stress

Results Groups

N.D N.D N.D N.D-d1/d3

Page 9: BDNF LTP Learning & Memory Voluntary wheel runningTreadmill running 1. Genetic differences 2. Effects of environment enrichment 3. Temporal relationship.

2h; -2d

Citrate synthase activity

BDNF mRNA levels

BDNF protein levels

Escape latency

Corticosterone levels

4-wk exercise training Mod. Exercise

Sev. Exercise with familiar.

Sev. Exercise without familiar.

Immobilization plus water

Acute Stress

Results Groups

N.D N.D N.D N.D-d1/d3

Page 10: BDNF LTP Learning & Memory Voluntary wheel runningTreadmill running 1. Genetic differences 2. Effects of environment enrichment 3. Temporal relationship.

2h; -2d

Citrate synthase activity

BDNF mRNA levels

BDNF protein levels

Escape latency

Corticosterone levels

4-wk exercise training Mod. Exercise

Sev. Exercise with familiar.

Sev. Exercise without familiar.

Immobilization plus water

Acute Stress

Results Groups

N.D N.D N.D N.D-d1/d3

2h; -2d

Page 11: BDNF LTP Learning & Memory Voluntary wheel runningTreadmill running 1. Genetic differences 2. Effects of environment enrichment 3. Temporal relationship.

2h; -2d

Citrate synthase activity

BDNF mRNA levels

BDNF protein levels

Escape latency

Corticosterone levels

4-wk exercise training Mod. Exercise

Sev. Exercise with familiar.

Sev. Exercise without familiar.

Immobilization plus water

Acute Stress

Results Groups

N.D N.D N.D N.D-d1/d3

2h;-2d d1/d3

Page 12: BDNF LTP Learning & Memory Voluntary wheel runningTreadmill running 1. Genetic differences 2. Effects of environment enrichment 3. Temporal relationship.

2h; -2d

Citrate synthase activity

BDNF mRNA levels

BDNF protein levels

Escape latency

Corticosterone levels

4-wk exercise training Mod. Exercise

Sev. Exercise with familiar.

Sev. Exercise without familiar.

Immobilization plus water

Acute Stress

Results Groups

N.D N.D N.D N.D-d1/d3

2h;-2d d1/d3

Page 13: BDNF LTP Learning & Memory Voluntary wheel runningTreadmill running 1. Genetic differences 2. Effects of environment enrichment 3. Temporal relationship.

0

10

20

30

40

50

60

C E

Esc

ape

late

ncy *

2h; -2d

Citrate synthase activity

BDNF mRNA levels

BDNF protein levels

Escape latency

Corticosterone levels

4-wk exercise training Mod. Exercise

Sev. Exercise with familiar.

Sev. Exercise without familiar.

Immobilization plus water

Acute Stress

Results Groups

N.D N.D N.D N.D-d1/d3

2h;-2d d1/d3

Page 14: BDNF LTP Learning & Memory Voluntary wheel runningTreadmill running 1. Genetic differences 2. Effects of environment enrichment 3. Temporal relationship.

2h; -2d

Citrate synthase activity

BDNF mRNA levels

BDNF protein levels

Escape latency

Corticosterone levels

4-wk exercise training Mod. Exercise

Sev. Exercise with familiar.

Sev. Exercise without familiar.

Immobilization plus water

Acute Stress

Results Groups

N.D N.D N.D N.D-d1/d3

2h;-2d d1/d3

0

10

20

30

40

50

60

C Stress

Esc

ape

late

ncy

(not sig.)N.D N.D N.D

Page 15: BDNF LTP Learning & Memory Voluntary wheel runningTreadmill running 1. Genetic differences 2. Effects of environment enrichment 3. Temporal relationship.

2h; -2d

Citrate synthase activity

BDNF mRNA levels

BDNF protein levels

Escape latency

Corticosterone levels

4-wk exercise training Mod. Exercise

Sev. Exercise with familiar.

Sev. Exercise without familiar.

Immobilization plus water

Acute Stress

Results Groups

N.D N.D N.D N.D-d1/d3

2h;-2d d1/d3 N.D N.D N.D

-N.D N.D?? N.D N.D

Page 16: BDNF LTP Learning & Memory Voluntary wheel runningTreadmill running 1. Genetic differences 2. Effects of environment enrichment 3. Temporal relationship.

1. 4-wk exercise training enhanced hippocampal BDNF mRNA and protein level at 2h after the last run but not after 2d.

Page 17: BDNF LTP Learning & Memory Voluntary wheel runningTreadmill running 1. Genetic differences 2. Effects of environment enrichment 3. Temporal relationship.

1. 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

Page 18: BDNF LTP Learning & Memory Voluntary wheel runningTreadmill running 1. Genetic differences 2. Effects of environment enrichment 3. Temporal relationship.

d1/d3

2h; -2d

2h;-2d

Citrate synthase activity

BDNF mRNA levels

BDNF protein levels

Escape latency

Corticosterone levels

4-wk exercise training Mod. Exercise

Sev. Exercise with familiar.

Sev. Exercise without familiar.

Immobilization plus water

Acute Stress

Results Groups

N.D N.D N.D N.D

-d1/d3

N.D N.D N.D

-N.D N.D N.D N.D

1. 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.

Page 19: BDNF LTP Learning & Memory Voluntary wheel runningTreadmill running 1. Genetic differences 2. Effects of environment enrichment 3. Temporal relationship.

d1/d3

2h; -2d

2h;-2d

Citrate synthase activity

BDNF mRNA levels

BDNF protein levels

Escape latency

Corticosterone levels

4-wk exercise training Mod. Exercise

Sev. Exercise with familiar.

Sev. Exercise without familiar.

Immobilization plus water

Acute Stress

Results Groups

N.D N.D N.D N.D

-d1/d3

N.D N.D N.D

-N.D N.D N.D N.D

2. Acute treadmill exercise, regardless of its intensity, may alter BDNF expression at the translational level or posttranslational level, whereas only high intensity or long-term exercise can

affect gene expression at the transcriptional level.

Page 20: BDNF LTP Learning & Memory Voluntary wheel runningTreadmill running 1. Genetic differences 2. Effects of environment enrichment 3. Temporal relationship.

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

d1/d3

2h; -2d

2h;-2d

Citrate synthase activity

BDNF mRNA levels

BDNF protein levels

Escape latency

Corticosterone levels

4-wk exercise training Mod. Exercise

Sev. Exercise with familiar.

Sev. Exercise without familiar.

Immobilization plus water

Acute Stress

Results Groups

N.D N.D N.D N.D

-d1/d3

N.D N.D N.D

-N.D N.D N.D N.D

Page 21: BDNF LTP Learning & Memory Voluntary wheel runningTreadmill running 1. Genetic differences 2. Effects of environment enrichment 3. Temporal relationship.

Really? - - - Run, run, run!