title: Exercise-induced improvement in cognitive performance after traumatic brain injury in rats is dependent on BDNF activation.
abstract: 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.
authors: Department of Neurosurgery, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095-7039, USA. ggriesbach@mednet.ucla.edu
authors: Grace Sophia
authors: GS
authors: Griesbach
authors: David Allen
authors: DA
authors: Hovda
authors: Fernando
authors: F
authors: Gomez-Pinilla
mesh_terms: 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
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D007136:Immunoglobulins; D016704:Synapsins