{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T23:33:08Z","timestamp":1790379188503,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T00:00:00Z","timestamp":1726704000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T00:00:00Z","timestamp":1726704000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      The accumulation and aggregation of beta\u2010amyloid (A\u03b2) peptides contributes to neuronal dysfunction and death. These A\u03b2 peptides originate from a transmembrane protein known as amyloid precursor protein (APP), which can be processed via two competing pathways. Alpha\u2010secretase (ADAM10) cleavage is thought to be neuroprotective while beta\u2010secretase (BACE1) cleavage results in the production of A\u03b2. Aerobic exercise reduces BACE1 activity, but the mechanisms involved are unknown though several exercise\u2010induced mediators such as lactate may be involved. The current study examined whether systemic lactate can alter APP processing and BACE1 and ADAM10 activity. Mice were randomly assigned to one of four groups (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a010 per group): (1) sedentary; (2) lactate\u2010injection (1.0\u00a0g\u00a0kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      body mass); (3) exercise; and (4) exercise and oxamate (lactate dehydrogenase inhibitor; 750\u00a0mg\u00a0kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      body mass). Two hours following intervention, the hippocampus and prefrontal cortex (PFC) were collected. In the PFC lactate\u2010injection and exercise resulted in higher ADAM10 activity compared to sedentary (exercise\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0215, lactate\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0038), in the hippocampus lactate\u2010injection was higher compared to sedentary (lactate\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.011), and this was absent in the presence of oxamate. Hippocampal BACE1 activity was lower in the lactate group compared to the exercise group (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.01). Oxamate resulted in higher BACE1 protein content compared to sedentary in the PFC (\n                      <jats:italic>vs<\/jats:italic>\n                      . sedentary\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.048). These findings suggest that lactate is important for regulating ADAM10 activity and thereby shifts APP processing away from A\u03b2 production.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp16327-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Exercise is known to alter the processing of amyloid precursor protein by reducing the activity of the rate\u2010limiting enzyme BACE1 and increasing the activity of ADAM10.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>It is thought that exercise\u2010induced factors are responsible for these enzymatic changes.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>This study examined if lactate accumulation plays a role in this process.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Mice were assigned to one of four groups: sedentary, lactate, exercise and exercise + lactate.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The findings demonstrate that lactate accumulation alters brain BACE1 and ADAM10 and shifts amyloid precursor protein processing away from beta\u2010amyloid production.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp286962","type":"journal-article","created":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T15:09:48Z","timestamp":1726758588000},"page":"5217-5228","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Lactate increases ADAM10 activity and reduces BACE1 activity in mouse brain"],"prefix":"10.1113","volume":"602","author":[{"given":"Isabel","family":"Moberg","sequence":"first","affiliation":[{"name":"Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth F.","family":"McCarthy","sequence":"additional","affiliation":[{"name":"Department of Kinesiology and Physical Education Wilfrid Laurier University  Waterloo Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Bellaflor","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Brock University  St. Catherines Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6902-5885","authenticated-orcid":false,"given":"Michael S.","family":"Finch","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Brock University  St. Catherines Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8135-4518","authenticated-orcid":false,"given":"Tom J.","family":"Hazell","sequence":"additional","affiliation":[{"name":"Department of Kinesiology and Physical Education Wilfrid Laurier University  Waterloo Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1577-2658","authenticated-orcid":false,"given":"Rebecca E. 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