Mild TBI gives rise to chronic depression-like behavior and associated alterations in glutamatergic protein expression in male Sprague Dawley rats

STUDY PURPOSE: The purpose of this study was to evaluate changes in depression-like behavior at 4, 8, and 12 weeks post-injury in male Sprague Dawley rats using a closed-head controlled cortical impact model of traumatic brain injury and relate behavioral changes to alterations in glutamatergic protein expression at 12 weeks. DATA COLLECTED: Closed-head controlled cortical impact (cCCI) was used to model mild traumatic brain injury in 12-week old male Sprague Dawley rats. Animals were randomly divided into sham (n=8) and injury (n=8) groups, where the injury group received a single impact at a velocity of 6 m/s, depth of 5 mm, and dwell time of 300 ms while anesthetized under isoflurane anesthesia. Animals had their heads shaved and a skull template was used to mark the site of impact over the right parietal cortex prior to impact. The Leica Impact One stereotaxic impactor was used to deliver the impact. The sham group underwent the same procedures but did not receive an impact. Righting response times were recorded following impact (or removal from anesthesia for sham animals). Body weights were recorded beginning on the date of impact testing and continued through 12 weeks. The splash test and the three-chamber sociability and social novelty tests were carried out at 4, 8, and 12 weeks post-injury to assess changes in self-care and social behaviors, respectively. Splash test outcomes included total duration of grooming, latency to begin grooming, and frequency of grooming. Sociability and social novelty behaviors were assessed using time spent in each chamber of the three-chamber arena and by a discrimination index calculated using time spent in chambers. Simple Western was used to assess protein expressional changes in N-methyl-D-aspartate receptor subunits GluN1, GluN2A, and GluN2B, in addition to glutamate transporter GLT-1, in the frontal cortex, hippocampus, and amygdala at 12 weeks post-injury. Protein expression data were represented as expression values normalized to the average sham expression value for each protein of interest. Statistical analyses including repeated measures ANOVA and unpaired t-tests were used to examine differences between groups, while linear regression analysis was utilized to measure relationships between behavioral metrics and protein expression. DATA USAGE NOTES: