Multi-Focal Neuronal Ultrastructural Abnormalities and Synaptic Alterations in Mice after Low-Intensity Blast Exposure

Landry M. Konan, Hailong Song, Genevieve Pentecost, Delvise Fogwe, Tina Ndam, Jiankun Cui, Catherine E. Johnson, De Ana Grant, Tommi White, Mei Chen, Weiming Xia, Ibolja Cernak, Ralph G. Depalma, Zezong Gu

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Service members during military actions or combat training are exposed frequently to primary blast generated by explosive weaponry. The majority of military-related neurotrauma are classified as mild and designated as "invisible injuries" that are prevalent during current conflicts. While the previous experimental blast injury studies using moderate- to high-intensity exposures focused mainly on gross and microscopic neuropathology, our previous studies have shown that low-intensity blast (LIB) exposures resulted in nanoscale subcellular myelin and mitochondrial damages and subsequent behavioral disorders in the absence of gross or detectable cellular damage. In this study, we used transmission electron microscopy to delineate the LIB effects at the ultrastructural level specifically focusing on the neuron perikaryon, axons, and synapses in the cortex and hippocampus of mice at seven and 30 days post-injury (DPI). We found dysmorphic dark neuronal perikaryon and "cytoplasmic aeration" of dendritic processes, as well as increased microtubular fragmentation of the myelinated axons along with biochemically measured elevated tau/phosphorylated tau/Aβ levels. The number of cortical excitatory synapses decreased along with a compensatory increase of the post-synaptic density (PSD) thickness both at seven and 30 DPI, while the amount of hippocampal CA1 synapses increased with the reduced PSD thickness. In addition, we observed a significant increase in protein levels of PSD95 and synaptophysin mainly at seven DPI indicating potential synaptic reorganization. These results demonstrated that a single LIB exposure can lead to ultrastructural brain injury with accompanying multi-focal neuronal organelle alterations. This pre-clinical study provides key insights into disease pathogenesis related to primary blast exposure.

Original languageEnglish (US)
Pages (from-to)2117-2128
Number of pages12
JournalJournal of Neurotrauma
Volume36
Issue number13
DOIs
StatePublished - Jul 1 2019

Keywords

  • axonal microtubule injury
  • low-intensity open-field blast
  • synaptic alterations
  • tau
  • transmission electron microscopy

ASJC Scopus subject areas

  • Clinical Neurology

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