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Journal Article

Citation

Patel MV, Sewell E, Dickson S, Kim H, Meaney D, Firestein BL. J. Neurotrauma 2019; ePub(ePub): ePub.

Affiliation

Rutgers The State University of New Jersey, 242612, Cell Biology and Neuroscience, Piscataway, New Jersey, United States ; firestein@biology.rutgers.edu.

Copyright

(Copyright © 2019, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2018.6291

PMID

30747034

Abstract

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

Keywords

DENDRITIC INJURY; MODELS OF INJURY; MOLECULAR BIOLOGICAL APPROACHES; TRAUMATIC BRAIN INJURY; controlled cortical impact

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