Temporal-specific sex and injury-dependent changes on neurogranin-associated synaptic signaling after controlled cortical impact in rats

Abstract

Abstract Extensive effort has been made to study the role of synaptic deficits in cognitive impairment after traumatic brain injury (TBI). Neurogranin (Ng) is a calcium-sensitive calmodulin (CaM)-binding protein essential for Ca2+/CaM-dependent kinase II (CaMKII) autophosphorylation which subsequently modulates synaptic plasticity. Given the loss of Ng expression after injury, additional research is warranted to discern changes in hippocampal post-synaptic signaling after TBI. Under isoflurane anesthesia, adult, male and female Sprague Dawley rats received a sham/control or controlled cortical impact (CCI) injury. Ipsilateral hippocampal synaptosomes were isolated at 24 hours, 1, 2 and 4 weeks post-injury and western blot was used to evaluate protein expression of Ng-associated signaling proteins. Two-way ANOVA was used to evaluate main effects of injury and sex at each time-point. There were significant injury and sex-dependent alterations in the hippocampal synaptic expression of Ng and associated synaptic proteins such as phosphorylated Ng, CaMKII, and CaM up to 4 weeks post-CCI, demonstrating TBI alters hippocampal post-synaptic signaling. This study furthers our understanding of mechanisms of cognitive dysfunction within the synapse sub-acutely after TBI.