title: Primary Blast Injury Depressed Hippocampal Long-Term Potentiation through Disruption of Synaptic Proteins.
abstract: Blast-induced traumatic brain injury (bTBI) is a major threat to United States service members in military conflicts worldwide. The effects of primary blast, caused by the supersonic shockwave interacting with the skull and brain, remain unclear. Our group has previously reported that in vitro primary blast exposure can reduce long-term potentiation (LTP), the electrophysiological correlate of learning and memory, in rat organotypic hippocampal slice cultures (OHSCs) without significant changes to cell viability or basal, evoked neuronal function. We investigated the time course of primary blast-induced deficits in LTP and the molecular mechanisms that could underlie these deficits. We found that pure primary blast exposure induced LTP deficits in a delayed manner, requiring longer than 1 hour to develop, and that these deficits spontaneously recovered by 10 days following exposure depending on blast intensity. Additionally, we observed that primary blast exposure reduced total α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor 1 (GluR1) subunit expression and phosphorylation of the GluR1 subunit at the serine-831 site. Blast also reduced the expression of postsynaptic density protein-95 (PSD-95) and phosphorylation of stargazin protein at the serine-239/240 site. Finally, we found that modulation of the cyclic adenosine monophosphate (cAMP) pathway ameliorated electrophysiological and protein-expression changes caused by blast. These findings could inform the development of novel therapies to treat blast-induced loss of neuronal function.
authors: 1 Department of Biomedical Engineering, Columbia University , New York, New York.
authors: Edward W
authors: EW
authors: Vogel
authors: 1 Department of Biomedical Engineering, Columbia University , New York, New York.
authors: Steve H
authors: SH
authors: Rwema
authors: 2 Department of Bioengineering, University of Pennsylvania , Philadelphia, Pennsylvania.
authors: David F
authors: DF
authors: Meaney
authors: 3 Department of Biomedical Engineering, Duke University , Durham, North Carolina.
authors: Cameron R Dale
authors: CR
authors: Bass
authors: 1 Department of Biomedical Engineering, Columbia University , New York, New York.
authors: Barclay
authors: B
authors: Morrison
mesh_terms: D000818:Animals; D001753:Blast Injuries / Q000150:complications*; D000070642:Brain Injuries, Traumatic / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology*; D015220:Calcium Channels / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology*; D017774:Long-Term Potentiation / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D000242:Cyclic AMP; D000076122:Disks Large Homolog 4 Protein; D018091:Receptors, AMPA; C491911:Cacng2 protein, rat; C501449:Dlg4 protein, rat
keywords: TBI; electrophysiology; in vitro studies; learning and memory; military injury