Neurogranin Protein Expression Is Reduced after Controlled Cortical Impact in Rats.

Traumatic brain injury (TBI) is known to cause short- and long-term synaptic changes in the brain, possibly underlying downstream cognitive impairments. Neuronal levels of neurogranin, a calcium-sensitive calmodulin-binding protein essential for synaptic plasticity and postsynaptic signaling, are correlated with cognitive function. This study aims to understand the effect of TBI on neurogranin by characterizing changes in protein expression at various time points after injury. Adult, male rats were subjected to either controlled cortical impact (CCI) or control surgery. Expression of neurogranin and post-synaptic density 95 (PSD-95) were evaluated by Western blot in the cortex and hippocampus at 24 h and 1, 2, and 4 weeks post-injury. We hypothesized that CCI reduces neurogranin levels in the cortex and hippocampus, and demonstrate different expression patterns from PSD-95. Neurogranin levels were reduced in the ipsilateral cortex and hippocampus up to 2 weeks after injury but recovered to sham levels by 4 weeks. The contralateral cortex and hippocampus were relatively resistant to changes in neurogranin expression post-injury. Qualitative immunohistochemical assessment corroborated the immunoblot findings. Particularly, the pericontusional cortex and ipsilateral Cornu Ammonis (CA)3 region showed marked reduction in immunoreactivity. PSD-95 demonstrated similar expression patterns to neurogranin in the cortex; however, in the hippocampus, protein expression was increased compared with sham at the 2 and 4 week time points. Our results indicate that CCI lowers neurogranin expression with temporal and regional specificity and that this occurs independently of dendritic loss. Further understanding of the role of neurogranin in synaptic biology after TBI will elucidate pathological mechanisms contributing to cognitive dysfunction.