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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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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
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.
How different treadmill exercise protocols would affect rat hippocampal BDNF gene expression?
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
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 *
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
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
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
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
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
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
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 *
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
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
Conclusions 4-wk exercise training enhanced hippocampal BDNF mRNA and protein level at 2h after the last run but not after 2d.
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
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 -
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
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.