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Introduction of these cytotoxic amyloids into the lateral ventricle impairs learning and memory in mice. However, it is unclear whether the amyloids of lung origin (1) are neurotropic, and (2) cause structural remodeling of hippocampal dendrites. Thus, we used electrophysiological studies in brain slices and structural analysis of post-mortem tissues obtained from animals exposed to endothelium-derived amyloids to assess these issues. The amyloids were administered via three different routes, by intracerebroventricular, intratracheal, and intraperitoneal injections. Synaptic long-term potentiation was abolished following intracerebroventricular amyloid injection. Fluorescence dialysis or Golgi-impregnation labeling showed reduced dendritic spine density and destabilized spines of hippocampal pyramidal neurons 4 weeks after intracerebroventricular amyloid injection. In comparison, endothelial amyloids introduced to the airway caused the most prominent dendritic spine density reduction, yet intraperitoneal injection of these amyloids did not affect spine density. Our findings indicate that infection-elicited lung endothelial amyloids are neurotropic and reduce neuronal dendritic spine density <jats:italic>in vivo<\/jats:italic>. Amyloids applied into the trachea may either be disseminated through the circulation and cross the blood-brain barrier to access the brain, initiate feed-forward amyloid transmissibility among cells of the blood-brain barrier or access the brain in other ways. Nevertheless, lung-derived amyloids suppress hippocampal signaling and cause injury to neuronal structure.<\/jats:p>","DOI":"10.1038\/s41598-020-66321-1","type":"journal-article","created":{"date-parts":[[2020,6,9]],"date-time":"2020-06-09T10:02:46Z","timestamp":1591696966000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Pneumonia-induced endothelial amyloids reduce dendritic spine density in brain neurons"],"prefix":"10.1038","volume":"10","author":[{"given":"Allison M.","family":"Scott","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandrea C.","family":"Jager","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meredith","family":"Gwin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Voth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron","family":"Balczon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Troy","family":"Stevens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike T.","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,6,9]]},"reference":[{"key":"66321_CR1","doi-asserted-by":"publisher","first-page":"1513","DOI":"10.1097\/CCM.0b013e3181e47be1","volume":"38","author":"TD Girard","year":"2010","unstructured":"Girard, T. 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