Glutamate Receptor Expression After Traumatic Brain Injury In A Rat Model Of Depression

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Maxon Knott
Noah Ziemba
Jennifer McGuire
Erika Correll
Laura Ngwenya

Abstract

By Maxon Knott, Neurobiology; Noah Ziemba, University of Pittsburgh; Jennifer McGuire, University of Cincinnati; Erika Correll, University of Massachusetts Amherst


Advisor: Laura Ngwenya


Abstract: Traumatic Brain Injury (TBI) patients with pre-existing psychiatric diagnoses have worse outcomes after TBI but are almost universally excluded from clinical TBI research. In order to study processes that impede recovery in vulnerable individuals, we used the Wistar-Kyoto (WKY) rat. The WKY strain has a behavioral phenotype that recapitulates aspects of human depression. Dysregulation of glutamate signaling is implicated in the etiology of multiple neurobehavioral disorders including major depression. We hypothesized that TBI would impact glutamate signalling more in the WKY rats than the Wistar (WIS) parent strain. We used the lateral fluid percussion model to induce TBI in adult male WKY and WIS rats, with sham controls for each strain. We used Western blotting to determine proteinlevels of_-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid(AMPA) receptor subunits, GluA1 and GluA2,N-methyl-D-aspartate(NMDA) receptor subunits, GluN2A and GluN2B, and the astrocytic glutamate transporter GLAST in the hippocampus 21 days after TBI. Western blot data were analyzed using two-way ANOVA. We found no effect of strain or TBI on expression of GluA1 or GluA2. Expression of GluN2Awas significantly higher in WKY than WIS rats (p=0.014) but was unaffected by TBI. GLAST expression was also higher in WKY rats (strain, p=0.0315) and not significantly altered by TBI. We found a significant effect of TBI (p=0.018) and an interaction of TBI and strain (p=0.005) on expression of GluN2B. GluN2B protein was significantly increased after TBI in WIS rats compared to WIS sham (p=0.0023) and both WKY groups (WKY sham, p=0.031; WKY TBI, p=0.017). Our data indicate that there are initial differences

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