1. UCLA, Brain Research Institute (LA)
Voluntary Exercise Induces a BDNF-Mediated Mechanism That Promotes Neuroplasticity
Fernando Gomez-Pinilla, Zeh Ting, Roland R. Roy, Raffaella Molteni, and V. Reggie Edgerton
UCLA, Brain Research Institute (LA)

2. Previous Findings BDNF Soleus
(Berchtold et al. 2001, 2002; Cotman and Berchtold 2002, 2006; Gomez-Pinilla et al. 2002)

3. Key Players
BDNF: modifies neuronal excitation and synaptic trasmission; important in memory formation and plasticity
trkB: 1° transmembrane receptor for BDNF w/ tyr kinase activity
Synapsin 1: phosphoprotein important for NT release
GAP-43: important for axonal growth and NT release
CREB: well-known txn factorregulates gene expression, specifically BDNF

4. Background
Botulinum toxin type A (BTX-A) purpose: determine effects of reducing NM output of single muscle on neurotrophin response to motor activity
Botulinum comes from Clostridium
Blocks release of Ach from NM jxns, thus preventing muscular contraction
Specifically degrades SNAP-25 (SNARE protein)

5. Botox

6. Hypothesis Plasticity
Exercise induces neuronal plasticity through BDNF and its receptor (trkB)
Studying neuromuscular system (hindlimb)
Plasticity
BDNF

7. Physical Parametrics Male Sprague-Dawley (rats) 3 months old
Individually housed
12/12 hour light/dark
Ad libitum food and wa-wa
Exercise cage (30x40x20 cm) with wheel
Adjustable resistance (1st day, no load…100g thereafter)
Carefully euthanized w/ pentobarb-Na+ and intracardial PBS and other goodies

8. Results

9. BDNF mRNA levels in spinal cord after 3 and 7 days of VE
Figure 1
+ correlation

10. BDNF immunohisto-quimica
Figure 2
Sedentary
Exercise
Lumbar spinal cord

11. Synapsin 1 (lumbar SC)
Figure 3

12. GAP-43 (lumbar SC)
Figure 4 (A,B)

13. CREB (lumbar SC)
Figure 4 (C,D)

14. Soleus Muscle BDNF mRNA BDNF Protein Synapsin 1 mRNA TrkB mRNA
Figure 5
BDNF mRNA
BDNF Protein
Synapsin 1 mRNA
TrkB mRNA

15. Effect of BTX-A Figure 6 Lumbar SC
Side ipsilateral to injection: decreased BDNF mRNA in sedentary and 7 days VE
Contralateral side: no change in sedentary, significant increase in 7 days VE
Soleus muscle
Ipsilateral: BDNF mRNA reduced in both sedentary and 7 days VE
Contralateral: no change sedentary, 175% increase with 7 days VE
Lumbar SC
Lumbar SC
Ipsilateral: decrease in sedentary rats, but maintained levels of synapsin 1 mRNA in 7 days VE
Contralateral: no change in sedentary synapsin 1 mRNA, significant increase in 7 days VE

16. Findings
BDNF, TrkB, Synapsin 1, GAP-43, and CREB mRNA increased with exercise in lumbar SC (also Synapsin 1 protein)
Direct relationship of mRNA levels to distance run (sed < 3d VE < 7d VE)
Interestingly, exercise maintained levels of synapsin 1 mRNA on ipsilateral side of BTX-A injection in lumbar SC

17. Findings (cont’d)
In soleus muscle, BDNF mRNA and protein levels increased (higher after 3 days VE than 7 days VE)
TrkB and Synapsin 1 mRNA levels increased after 3 days VE and returned to control levels after 7 days VE
No change in GAP-43 mRNA seen in VE groups

18. Findings (cont’d) Effect of BTX-A injection:
Decrease in BDNF mRNA in lumbar SC and soleus muscle on ipsilateral side in sedentary and VE
Decrease in Synapsin 1 mRNA in lumbar SC on ipsilateral side in sedentary and VE
Increase seen on contralateral side of soleus and lumbar SC in VE group (BDNF and Synapsin 1 mRNA)
Interestingly, VE maintained levels of synapsin 1 mRNA on ipsilateral side of BTX-A injection in lumbar SC

19. Acknowledgements
Niel Burns
sustenance
Diet Mt Dew
Meeko