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During viral encephalitis, these cells undergo dynamic changes that can reflect layer\u2010specific vulnerability. In this study, we characterized whether astrocytes from different CA3 hippocampal layers display distinct morphological responses to Piry virus\u2010induced encephalitis. Adult female Swiss mice were intranasally inoculated with the Piry virus and sacrificed at 20\u2010 or 40\u2010days post\u2010infection (dpi). GFAP+ astrocytes from the\n                    <jats:italic>Stratum lacunosum\u2010moleculare<\/jats:italic>\n                    (SLM) and\n                    <jats:italic>Stratum oriens<\/jats:italic>\n                    (SO) were three\u2010dimensionally reconstructed. Morphometric data were evaluated using hierarchical clustering, linear discriminant analysis (LDA), and generalized linear models. Immunohistochemistry confirmed widespread viral neuroinvasion across olfactory and limbic regions. Hierarchical clustering identified 3\u20134 morphotypes per layer and time point with robust internal consistency, and LDA validated cluster assignments with high accuracy (&gt;\u200991%). At 20\u2009dpi, SLM astrocytes displayed significantly greater morphological complexity than SO astrocytes, whereas at 40\u2009dpi responses were more heterogeneous, indicating temporal diversification of astrocytic reactivity. These findings provide an observational description of layer\u2010 and time\u2010dependent astrocyte morphological plasticity during viral encephalitis. They underscore the value of morphometric and multivariate analyses for dissecting glial heterogeneity, while highlighting the need for future studies to determine the functional significance of these morphotypes.\n                  <\/jats:p>","DOI":"10.1002\/hipo.70085","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T04:30:32Z","timestamp":1771821032000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Layer\u2010Specific Astrocyte Morphological Responses in the\n                    <scp>CA3<\/scp>\n                    Hippocampus Region During Piry Virus\u2010Induced Encephalitis"],"prefix":"10.1002","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6798-3142","authenticated-orcid":false,"given":"Diego","family":"de Almeida Miranda","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Investiga\u00e7\u00f5es em Neurodegenera\u00e7\u00e3o e Infec\u00e7\u00e3o Universidade Federal do Par\u00e1, Instituto de Ci\u00eancias Biol\u00f3gicas, Hospital Universit\u00e1rio Jo\u00e3o de Barros Barreto  Bel\u00e9m Par\u00e1 Brazil"},{"name":"Laborat\u00f3rio de Biologia Molecular e Neuroecologia Instituto Federal de Educa\u00e7\u00e3o Ci\u00eancia e Tecnologia do Par\u00e1, Campus Bragan\u00e7a  Bragan\u00e7a Par\u00e1 Brazil"}]},{"given":"Aline Andrade","family":"de Sousa","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Investiga\u00e7\u00f5es em Neurodegenera\u00e7\u00e3o e Infec\u00e7\u00e3o Universidade Federal do Par\u00e1, Instituto de Ci\u00eancias Biol\u00f3gicas, Hospital Universit\u00e1rio Jo\u00e3o de Barros Barreto  Bel\u00e9m Par\u00e1 Brazil"}]},{"given":"Renata Rodrigues","family":"dos Reis","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Investiga\u00e7\u00f5es em Neurodegenera\u00e7\u00e3o e Infec\u00e7\u00e3o Universidade Federal do Par\u00e1, Instituto de Ci\u00eancias Biol\u00f3gicas, Hospital Universit\u00e1rio Jo\u00e3o de Barros Barreto  Bel\u00e9m Par\u00e1 Brazil"}]},{"given":"Zaire Alves","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Microscopia Eletr\u00f4nica Instituto Evandro Chagas, Se\u00e7\u00e3o de Hepatologia  Bel\u00e9m Par\u00e1 Brazil"}]},{"given":"Jos\u00e9 Antonio Pican\u00e7o","family":"Diniz","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Microscopia Eletr\u00f4nica Instituto Evandro Chagas, Se\u00e7\u00e3o de Hepatologia  Bel\u00e9m Par\u00e1 Brazil"}]},{"given":"Pedro Fernando","family":"da Costa Vasconcelos","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias Biol\u00f3gicas e da Sa\u00fade Universidade do Estado do Par\u00e1  Bel\u00e9m Par\u00e1 Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4395-6964","authenticated-orcid":false,"given":"Cristovam Guerreiro","family":"Diniz","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Molecular e Neuroecologia Instituto Federal de Educa\u00e7\u00e3o Ci\u00eancia e Tecnologia do Par\u00e1, Campus Bragan\u00e7a  Bragan\u00e7a Par\u00e1 Brazil"}]},{"given":"Daniel Clive","family":"Anthony","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Laboratory of Experimental Neuropathology University of Oxford  Oxford England UK"}]},{"given":"Dora","family":"Brites","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy Universidade de Lisboa, Research Institute for Medicines (iMed.ULisboa)  Lisbon Portugal"},{"name":"Department of Biochemistry and Human Biology, Faculty of Pharmacy Universidade de Lisboa  Lisbon Portugal"}]},{"given":"Cristovam Wanderley Pican\u00e7o","family":"Diniz","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Investiga\u00e7\u00f5es em Neurodegenera\u00e7\u00e3o e Infec\u00e7\u00e3o Universidade Federal do Par\u00e1, Instituto de Ci\u00eancias Biol\u00f3gicas, Hospital Universit\u00e1rio Jo\u00e3o de Barros Barreto  Bel\u00e9m Par\u00e1 Brazil"}]},{"given":"Daniel Guerreiro","family":"Diniz","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Investiga\u00e7\u00f5es em Neurodegenera\u00e7\u00e3o e Infec\u00e7\u00e3o Universidade Federal do Par\u00e1, Instituto de Ci\u00eancias Biol\u00f3gicas, Hospital Universit\u00e1rio Jo\u00e3o de Barros Barreto  Bel\u00e9m Par\u00e1 Brazil"},{"name":"Laborat\u00f3rio de Microscopia Eletr\u00f4nica Instituto Evandro Chagas, Se\u00e7\u00e3o de Hepatologia  Bel\u00e9m Par\u00e1 Brazil"},{"name":"N\u00facleo de Pesquisas em Oncologia Universidade Federal do Par\u00e1, Hospital Universit\u00e1rio Jo\u00e3o de Barros Barreto  Bel\u00e9m Par\u00e1 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