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However, the biological mechanisms by which physical exercise modulates dementia and Alzheimer's disease (AD) progression are still unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study investigated whether long-term (6 months) of voluntary wheel running induces neuroprotective effects in the pathogenesis of AD in middle-aged (8 months) female mice, focusing on energy metabolism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A genetic mice model of AD (3xTg-AD) that performed wheel running presented changes in body metabolism and muscle oxidative profile, as well as restored discriminative and non-associative retention memories, evaluated by novel object recognition and open field tasks, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the hippocampus, these mice exhibited reduced levels of amyloidogenic A\u03b2PP\u03b2 fragment, phospho-Tau protein and phospho-Akt (activated form), without changes in phospho-AMPK (activated form). In addition, hippocampal mitochondria presented a restored respiratory function, characterized by lower coupling degree and weak contribution from complex I found in 3xTg-AD mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The results demonstrated that voluntary exercise improves cognitive parameters and biochemical hallmarks of AD, modulates Akt activation and enhances mitochondrial energy metabolism in hippocampus of middle-aged 3xTg-AD female mice, thereby reinforcing the neuroprotective role of physical exercise and the involvement of mitochondria in the etiology of the AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877241289388","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T01:53:02Z","timestamp":1732499582000},"page":"424-436","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Voluntary wheel running decreases amyloidogenic pathway and rescues cognition and mitochondrial energy metabolism in middle-aged female 3xTg-AD mouse model of Alzheimer's disease"],"prefix":"10.1177","volume":"102","author":[{"given":"Jonathas Rodrigo","family":"dos Santos","sequence":"first","affiliation":[{"name":"Department of Biomolecular Sciences, School of Pharmaceutical Sciences of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Ribeir\u00e3o Preto, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Henrique Rocha","family":"Catal\u00e3o","sequence":"additional","affiliation":[{"name":"Department of Psychology, Faculty of Philosophy, Sciences and Letters of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Ribeir\u00e3o Preto, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anderson","family":"Vulczak","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences, School of Pharmaceutical Sciences of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Ribeir\u00e3o Preto, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Elisa Caleiro Seixas","family":"Azzolini","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences, School of Pharmaceutical Sciences of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Ribeir\u00e3o Preto, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7464-9385","authenticated-orcid":false,"given":"Luciane Carla","family":"Alberici","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences, School of Pharmaceutical Sciences of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Ribeir\u00e3o Preto, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2024,10,29]]},"reference":[{"key":"e_1_3_4_2_2","unstructured":"World Health Organization. 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