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Accumulating preclinical evidence suggests that ontogenic FLX exposure leads to deregulated affect-related phenotypes in adulthood. Mood-related symptomatology constitutes a risk-factor for various neurological disorders, including Alzheimer\u2019s disease (AD), making it possible for juvenile FLX history to exacerbate the development of neurodegenerative diseases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>Because AD is characterized by the pathological accumulation of hyperphosphorylated tau, which can result from impaired function of protein degradation pathways, such as autophagy and the ubiquitin-proteasome system (UPS), we evaluated the long-term effects of adolescent FLX exposure on these pathways, using mice as a model system.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We subjected C57BL\/6 adolescent male mice to FLX (20\u200amg\/kg\/day) from postnatal day (PD) 35 to PD49. Twenty-one days after the last FLX injection (i.e., adulthood; PD70), mice were euthanized and, using immunoblotting analysis, we evaluated protein markers of autophagy (Beclin-1, LC3-II, p62) and the UPS (K48-pUb), as well as AD-associated forms of phosphorylated tau, within the hippocampus and prefrontal cortex.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Juvenile FLX pre-exposure mediated long-term changes in the expression of protein markers (increased LC3-II and decreased p62) that is consistent with autophagy activation, particularly in the prefrontal cortex. Furthermore, FLX history induced persistent accumulation of AD-associated variants of tau in both the hippocampus and prefrontal cortex<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Adolescent FLX treatment may have enduring effects in the neuronal protein degradation machinery, which could adversely influence clearance of abnormal proteins, potentially predisposing individuals to developing AD in later life.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jad-210475","type":"journal-article","created":{"date-parts":[[2021,8,20]],"date-time":"2021-08-20T12:27:36Z","timestamp":1629462456000},"page":"1691-1702","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":11,"title":["Autophagy Induction and Accumulation of Phosphorylated Tau in the Hippocampus and Prefrontal Cortex of Adult C57BL\/6 Mice Subjected to Adolescent Fluoxetine Treatment"],"prefix":"10.1177","volume":"83","author":[{"given":"Jorge A.","family":"Sierra-Fonseca","sequence":"first","affiliation":[{"name":"The University of Texas at El Paso","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minerva","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"The University of Texas at El Paso","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anapaula","family":"Themann","sequence":"additional","affiliation":[{"name":"The University of Texas at El Paso","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Lira","sequence":"additional","affiliation":[{"name":"The University of Texas at El Paso","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco J.","family":"Flores-Ramirez","sequence":"additional","affiliation":[{"name":"The University of Texas at El Paso","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Vargas-Medrano","sequence":"additional","affiliation":[{"name":"Texas Tech University Health Science Center","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bharathi S.","family":"Gadad","sequence":"additional","affiliation":[{"name":"Texas Tech University Health Science Center","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio D.","family":"I\u00f1iguez","sequence":"additional","affiliation":[{"name":"The University of Texas at El Paso","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2021,8,20]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyg.2019.00543"},{"key":"e_1_3_2_3_2","first-page":"537","article-title":"Depression: A major public health problem in need of a multi-sectoral response","volume":"136","author":"Jacob KS","year":"2012","unstructured":"JacobKS (2012) Depression: A major public health problem in need of a multi-sectoral response. 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