%0 Journal Article %T A role for postsynaptic density 95 and its binding partners in models of traumatic brain injury %J Journal of neurotrauma %D 2019 %A Patel, Mihir V. %A Sewell, Emily %A Dickson, Samantha %A Kim, Hyuck %A Meaney, David %A Firestein, Bonnie L. %V 36 %N 13 %P 2129-2138 %X Postsynaptic density 95 (PSD-95), the major scaffold protein at excitatory synapses, plays a major role in mediating intracellular signaling by synaptic N-methyl-D-aspartate (NMDA) type glutamate receptors. Despite the fact that much is known about the role of PSD-95 in NMDA-mediated toxicity, less is known about its role in mechanical injury, and more specifically, in traumatic brain injury. Given that neural circuitry is disrupted after TBI and that PSD-95 and its interactors end-binding protein 3 (EB3) and adenomatous polyposis coli (APC) shape dendrites, we examined whether changes to these proteins and their interactions occur after brain trauma. Here, we report that total levels of PSD-95 and the interaction of PSD-95 with EB3 increase at 1 and 7 days after moderate CCI, but these changes do not occur after mild injury. Since changes occur to PSD-95 following brain trauma in vivo, we next considered the functional consequences of PSD-95 alterations in vitro. Rapid deformation of cortical neurons leads to neuronal death 72h after injury, but this outcome is not dependent on PSD-95 expression. However, disruptions in dendritic arborization following stretch injury in vitro require PSD-95 expression, and these changes in arborization can be mimicked with expression of PSD-95 mutants lacking the second PDZ domain. Thus, PSD-95 and its interactors may serve as therapeutic targets for repairing dendrites after TBI.

Language: en

%G en %I Mary Ann Liebert Publishers %@ 0897-7151 %U http://dx.doi.org/10.1089/neu.2018.6291