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Neurological complications following a blast injury, including depression, anxiety, and memory problems, often persist even when brain damage is undetectable. Here, hippocampal explants were exposed to the explosive 1,3,5\u2010trinitro\u20101,3,5\u2010triazinane (RDX) to identify indicators of blast\u2010induced changes within important neuronal circuitries. Highly controlled detonations of small, 1.7\u2010gram RDX spherical charges reduced synaptic markers known to be downregulated in cognitive disorders, but without causing overt neuronal loss or astroglial responses. In the absence of neuromorphological alterations, levels of synaptophysin, GluA1, and synapsin IIb were significantly diminished within 24\u00a0hr, and these synaptic components exhibited progressive reductions following blast exposure as compared to their stable maintenance in control explants. In contrast, labeling of the synapsin IIa isoform remained unaltered, while neuropilar staining of other markers decreased, including synapsin IIb and neural cell adhesion molecule (NCAM) isoforms, along with evidence of NCAM proteolytic breakdown. NCAM<jats:sub>180<\/jats:sub> displayed a distinct decline after the RDX blasts, whereas NCAM<jats:sub>140<\/jats:sub> and NCAM<jats:sub>120<\/jats:sub> exhibited smaller or no deterioration, respectively. Interestingly, the extent of synaptic marker reduction correlated with AT8\u2010positive tau levels, with tau pathology stochastically found in CA1 neurons and their dendrites. The decline in synaptic components was also reflected in the size of evoked postsynaptic currents recorded from CA1 pyramidals, which exhibited a severe and selective reduction. The identified indicators of blast\u2010mediated synaptopathy point to the need for early biomarkers of explosives altering synaptic integrity with links to dementia risk, to advance strategies for both cognitive health and therapeutic monitoring.<\/jats:p>","DOI":"10.1111\/bpa.12936","type":"journal-article","created":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T06:31:30Z","timestamp":1614234690000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Distinct and dementia\u2010related synaptopathy in the hippocampus after military blast exposures"],"prefix":"10.1111","volume":"31","author":[{"given":"Michael F.","family":"Almeida","sequence":"first","affiliation":[{"name":"Biotechnology Research and Training Center University of North Carolina\u2014Pembroke Pembroke NC 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USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serena M.","family":"Dudek","sequence":"additional","affiliation":[{"name":"Neurobiology Laboratory National Institute of Environmental Health Sciences Research Triangle Park NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher J.","family":"Norton","sequence":"additional","affiliation":[{"name":"Biotechnology Research and Training Center University of North Carolina\u2014Pembroke Pembroke NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine M.","family":"Parisian","sequence":"additional","affiliation":[{"name":"Biotechnology Research and Training Center University of North Carolina\u2014Pembroke Pembroke NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen L.G.","family":"Farizatto","sequence":"additional","affiliation":[{"name":"Biotechnology Research and Training Center University of North Carolina\u2014Pembroke Pembroke NC 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