title: Controlled contusion injury alters molecular systems associated with cognitive performance.
abstract: We investigated whether a learning impairment after a controlled cortical impact (CCI) injury was associated with alterations in molecules involved in synaptic plasticity and learning and memory. Adult male rats with moderate CCI to the left parietal cortex, tested in a Morris water maze (MWM) beginning at postinjury day 10, showed impaired cognitive performance compared with sham-treated rats. Tissue was extracted for mRNA analysis on postinjury day 21. The expression of brain-derived neurotrophic factor (BDNF), synapsin I, cyclic-AMP response element binding protein (CREB), and calcium-calmodulin-dependent protein kinase II (alpha-CAMKII) were all significantly decreased compared with sham injury levels within the ipsilateral hippocampus after CCI. No significant molecular level changes were found in the contralateral hippocampus. Decreased expression of BDNF and synapsin I was also found within the ipsilateral parietal cortex of CCI-injured rats compared with shams. However, BDNF and synapsin I expressions were significantly increased in the contralateral parietal cortex of the CCI rats. CREB expression was significantly decreased within the contralateral cortex of the CCI group. These findings show enduring reductions in the expression of BDNF, synapsin I, CREB, and alpha-CAMKII ipsilateral to a CCI injury, which seem associated with the spatial learning deficits observed in this injury model. In addition, the delayed increase in the expression of BDNF and synapsin I within the cortex contralateral to CCI may reflect restorative processes in areas homotypical to the injury.
authors.affiliation: Department of Neurosurgery, University of California, Los Angeles, California 90024-7039, USA. ggriesbach@mednet.ucla.edu
authors.forename: Grace Sophia
authors.initials: GS
authors.lastname: Griesbach
authors.forename: Richard L
authors.initials: RL
authors.lastname: Sutton
authors.forename: David A
authors.initials: DA
authors.lastname: Hovda
authors.forename: Zhe
authors.initials: Z
authors.lastname: Ying
authors.forename: Fernando
authors.initials: F
authors.lastname: Gomez-Pinilla
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000503:physiopathology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002540:Cerebral Cortex / Q000503:physiopathology; D003071:Cognition / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D015870:Gene Expression; D006624:Hippocampus / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D010296:Parietal Lobe / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016704:Synapsins / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D012333:RNA, Messenger; D016704:Synapsins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2