Exercise-induced improvement in cognitive performance after traumatic brain injury in rats is dependent on BDNF activation.
We have previously shown that voluntary exercise upregulates brain derived neurotrophic factor (BDNF) within the hippocampus and is associated with an enhancement of cognitive recovery after a lateral fluid percussion injury (FPI). In order to determine if BDNF is critical to this effect we used an immunoadhesin chimera (TrkB-IgG) that inactivates free BDNF. This BDNF inhibitor was administered to adult male rats two weeks after they had received a mild fluid percussion injury (FPI) or sham surgery. These animals were then housed with or without access to a running wheel (RW) from post-injury-day (PID) 14 to 20. On PID 21, rats were tested for spatial learning in a Morris Water Maze. Results showed that exercise counteracted the cognitive deficits associated with the injury. However this exercise-induced cognitive improvement was attenuated in the FPI-RW rats that were treated with TrkB-IgG. Molecules important for synaptic plasticity and learning were measured in a separate group of rats that were sacrificed immediately after exercise (PID 21). Western blot analyses showed that exercise increased the mature form of BDNF, synapsin I and cyclic-AMP response-element-binding protein (CREB) in the vehicle treated Sham-RW group. However, only the mature form of BDNF and CREB were increased in the vehicle treated FPI-RW group. Blocking BDNF (pre administration of TrkB-IgG) greatly reduced the molecular effects of exercise in that exercise-induced increases of BDNF, synapsin I and CREB were not observed. These studies provide evidence that BDNF has a major role in exercise's cognitive effects in traumatically injured brain.
Griesbach
Grace Sophia
GS
Department of Neurosurgery, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095-7039, USA. ggriesbach@mednet.ucla.edu
Hovda
David Allen
DA
Gomez-Pinilla
Fernando
F
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D001930:Brain Injuries / Q000378:metabolism* / Q000503:physiopathology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003071:Cognition / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology; D007136:Immunoglobulins / Q000008:administration & dosage; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008863:Microspheres; D010766:Phosphorylation; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016704:Synapsins / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D007136:Immunoglobulins; D016704:Synapsins