TY  - JOUR
PY  - 2019//
TI  - A role for postsynaptic density 95 and its binding partners in models of traumatic brain injury
JO  - Journal of neurotrauma
A1  - Patel, Mihir V.
A1  - Sewell, Emily
A1  - Dickson, Samantha
A1  - Kim, Hyuck
A1  - Meaney, David
A1  - Firestein, Bonnie L.
SP  - 2129
EP  - 2138
VL  - 36
IS  - 13
N2  - 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.<p />  <p>Language: en</p>
LA  - en
SN  - 0897-7151
UR  - http://dx.doi.org/10.1089/neu.2018.6291
ID  - ref1
ER  -