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To determine whether changes in dendritic architecture might underlie the neurocognitive sequelae found after irradiation, we investigated the impact of cranial irradiation (1 and 10 Gy) on a range of micromorphometric parameters in mice 10 and 30 d following exposure. Our data revealed significant reductions in dendritic complexity, where dendritic branching, length, and area were routinely reduced (&gt;50%) in a dose-dependent manner. At these same doses and times we found significant reductions in the number (20\u201335%) and density (40\u201370%) of dendritic spines on hippocampal neurons of the dentate gyrus. Interestingly, immature filopodia showed the greatest sensitivity to irradiation compared with more mature spine morphologies, with reductions of 43% and 73% found 30 d after 1 and 10 Gy, respectively. Analysis of granule-cell neurons spanning the subfields of the dentate gyrus revealed significant reductions in synaptophysin expression at presynaptic sites in the dentate hilus, and significant increases in postsynaptic density protein (PSD-95) were found along dendrites in the granule cell and molecular layers. These findings are unique in demonstrating dose-responsive changes in dendritic complexity, synaptic protein levels, spine density and morphology, alterations induced in hippocampal neurons by irradiation that persist for at least 1 mo, and that resemble similar types of changes found in many neurodegenerative conditions.<\/jats:p>","DOI":"10.1073\/pnas.1307301110","type":"journal-article","created":{"date-parts":[[2013,7,15]],"date-time":"2013-07-15T21:07:37Z","timestamp":1373922457000},"page":"12822-12827","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":237,"title":["Cranial irradiation compromises neuronal architecture in the hippocampus"],"prefix":"10.1073","volume":"110","author":[{"given":"Vipan Kumar","family":"Parihar","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, University of California, Irvine, CA 92697-2695"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles L.","family":"Limoli","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of California, Irvine, CA 92697-2695"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2013,7,15]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11864-006-0026-5"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2012.02.004"},{"key":"e_1_3_3_3_2","first-page":"75","article-title":"Neurocognitive dysfunction in cancer patients","volume":"14","author":"Meyers CA","year":"2000","unstructured":"CA Meyers, Neurocognitive dysfunction in cancer patients. 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