{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T03:01:19Z","timestamp":1790218879779,"version":"4.1.0"},"reference-count":75,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,30]],"date-time":"2020-12-30T00:00:00Z","timestamp":1609286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>We previously demonstrated, using the Piry virus model, that environmental enrichment promotes higher T-cell infiltration, fewer microglial changes, and faster central nervous system (CNS) virus clearance in adult mice. However, little is known about disease progression, behavioral changes, CNS cytokine concentration, and neuropathology in limbic encephalitis in experimental models. Using Cocal virus, we infected C57Bl6 adult mice and studied the neuroanatomical distribution of viral antigens in correlation with the microglial morphological response, measured the CNS cytokine concentration, and assessed behavioral changes. C57Bl6 adult mice were maintained in an impoverished environment (IE) or enriched environment (EE) for four months and then subjected to the open field test. Afterwards, an equal volume of normal or virus-infected brain homogenate was nasally instilled. The brains were processed to detect viral antigens and microglial morphological changes using selective immunolabeling. We demonstrated earlier significant weight loss and higher mortality in IE mice. Additionally, behavioral analysis revealed a significant influence of the environment on locomotor and exploratory activity that was associated with less neuroinvasion and a reduced microglial response. Thus, environmental enrichment was associated with a more effective immune response in a mouse model of limbic encephalitis, allowing faster viral clearance\/decreased viral dissemination, reduced disease progression, and less CNS damage.<\/jats:p>","DOI":"10.3390\/v13010048","type":"journal-article","created":{"date-parts":[[2020,12,30]],"date-time":"2020-12-30T20:13:41Z","timestamp":1609359221000},"page":"48","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Limbic Encephalitis Brain Damage Induced by Cocal Virus in Adult Mice Is Reduced by Environmental Enrichment: Neuropathological and Behavioral Studies"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9519-5047","authenticated-orcid":false,"given":"Priscilla","family":"Freitas","sequence":"first","affiliation":[{"name":"Instituto Evandro Chagas, Unidade de Microscopia Eletr\u00f4nica, Avenida Almirante Barroso, 492, Bairro do Marco, CEP 66.093-020 Bel\u00e9m, Par\u00e1, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Lima","sequence":"additional","affiliation":[{"name":"Instituto Evandro Chagas, Unidade de Microscopia Eletr\u00f4nica, Avenida Almirante Barroso, 492, Bairro do Marco, CEP 66.093-020 Bel\u00e9m, Par\u00e1, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Instituto Evandro Chagas, Unidade de Microscopia Eletr\u00f4nica, Avenida Almirante Barroso, 492, Bairro do Marco, CEP 66.093-020 Bel\u00e9m, Par\u00e1, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6457-0067","authenticated-orcid":false,"given":"Tatyane","family":"Cabral","sequence":"additional","affiliation":[{"name":"Instituto Evandro Chagas, Unidade de Microscopia Eletr\u00f4nica, Avenida Almirante Barroso, 492, Bairro do Marco, CEP 66.093-020 Bel\u00e9m, Par\u00e1, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4843-1216","authenticated-orcid":false,"given":"Alexandre","family":"Farias","sequence":"additional","affiliation":[{"name":"Instituto Evandro Chagas, Unidade de Microscopia Eletr\u00f4nica, Avenida Almirante Barroso, 492, Bairro do Marco, CEP 66.093-020 Bel\u00e9m, Par\u00e1, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5016-392X","authenticated-orcid":false,"given":"Ana","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Instituto Evandro Chagas, Unidade de Microscopia Eletr\u00f4nica, Avenida Almirante Barroso, 492, Bairro do Marco, CEP 66.093-020 Bel\u00e9m, Par\u00e1, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7369-2165","authenticated-orcid":false,"given":"Daniel","family":"Diniz","sequence":"additional","affiliation":[{"name":"Instituto Evandro Chagas, Unidade de Microscopia Eletr\u00f4nica, Avenida Almirante Barroso, 492, Bairro do Marco, CEP 66.093-020 Bel\u00e9m, Par\u00e1, Brazil"},{"name":"Laborat\u00f3rio de Investiga\u00e7\u00f5es em Neurodegenera\u00e7\u00e3o e Infec\u00e7\u00e3o no Hospital Universit\u00e1rio Jo\u00e3o de Barros Barreto, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal do Par\u00e1, Rua dos Mundurucus, Bairro do Guam\u00e1, 4487, CEP 66.073-005 Bel\u00e9m, Par\u00e1, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6611-6880","authenticated-orcid":false,"given":"Cristovam","family":"Pican\u00e7o Diniz","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Investiga\u00e7\u00f5es 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