voluntary exercise induces a bdnf- mediated mechanism that promotes neuroplasticity fernando...
TRANSCRIPT
Voluntary Exercise Induces a BDNF-Voluntary Exercise Induces a BDNF-Mediated Mechanism That Promotes Mediated Mechanism That Promotes
NeuroplasticityNeuroplasticity
Fernando Gomez-Pinilla, Zeh Ting, Roland R. Roy, Fernando Gomez-Pinilla, Zeh Ting, Roland R. Roy, Raffaella Molteni, and V. Reggie EdgertonRaffaella Molteni, and V. Reggie Edgerton
UCLA, Brain Research Institute (LA)UCLA, Brain Research Institute (LA)
Previous FindingsPrevious Findings
BDNF
(Berchtold et al. 2001, 2002; Cotman and Berchtold 2002, 2006; Gomez-Pinilla et al. 2002)
Soleus
Key PlayersKey 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 factorregulates gene expression, specifically BDNF
BackgroundBackground
• 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)
HypothesisHypothesis
• Exercise induces neuronal plasticity through BDNF and its receptor (trkB)– Studying neuromuscular system (hindlimb)
BDNF Plasticity
Physical ParametricsPhysical 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
BDNF mRNA levels in spinal cord BDNF mRNA levels in spinal cord after 3 and 7 days of VEafter 3 and 7 days of VE
Figure 1
+ correlation
Effect of BTX-AEffect of BTX-ASide ipsilateral to injection: decreased BDNF
mRNA in sedentary and 7 days VE
Contralateral side: no change in sedentary, significant increase in 7 days VE
Lumbar SC
Soleus muscleIpsilateral: BDNF mRNA reduced in both
sedentary and 7 days VE
Contralateral: no change sedentary, 175% increase with 7 days VE
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
Lumbar SCLumbar SC
Figure 6
FindingsFindings
• 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
Findings (cont’d)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
Findings (cont’d)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