Proteomic Changes in the Hippocampus after Repeated Explosive-Driven Blasts

Diego Iacono, Kathleen Hatch, Erin K. Murphy, Robert N. Cole, Jeremy Post, Fabio Leonessa, Daniel P. Perl

Research output: Contribution to journalArticlepeer-review

Abstract

Repeated blast-traumatic brain injury (blast-TBI) has been hypothesized to cause persistent and unusual neurological and psychiatric symptoms in service members returning from war zones. Blast-wave primary effects have been supposed to induce damage and molecular alterations in the brain. However, the mechanisms through which the primary effect of an explosive-driven blast wave generate brain lesions and induce brain consequences are incompletely known. Prior findings from rat brains exposed to two consecutive explosive-driven blasts showed molecular changes (hyperphosphorylated-Tau, AQP4, S100β, PDGF, and DNA-polymerase-β) that varied in magnitude and direction across different brain regions. We aimed to compare, in an unbiased manner, the proteomic profile in the hippocampus of double blast vs sham rats using mass spectrometry (MS). Data showed differences in up- and down-regulation for protein abundances in the hippocampus of double blast vs sham rats. Tandem mass tag (TMT)-MS results showed 136 up-regulated and 94 down-regulated proteins between the two groups (10.25345/C52B8VP0X). These TMT-MS findings revealed changes never described before in blast studies, such as increases in MAGI3, a scaffolding protein at cell-cell junctions, which were confirmed by Western blotting analyses. Due to the absence of behavioral and obvious histopathological changes as described in our previous publications, these proteomic data further support the existence of an asymptomatic blast-induced molecular altered status (ABIMAS) associated with specific protein changes in the hippocampus of rats repeatedly expsosed to blast waves generated by explosive-driven detonations.

Original languageEnglish (US)
Pages (from-to)397-408
Number of pages12
JournalJournal of proteome research
Volume23
Issue number1
DOIs
StatePublished - Jan 5 2024

Keywords

  • asymptomatic blast-induced molecular altered status
  • blast wave primary effects
  • explosive-driven blasts
  • hippocampus
  • membrane-associated guanylate kinase inverted 3 (MAGI3)
  • repeated blast exposure
  • tandem mass tag proteomics
  • traumatic brain injury

ASJC Scopus subject areas

  • General Chemistry
  • Biochemistry

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