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An additional group of mice on standard chow received saline vehicle. Energy intake, body weight, glucose and insulin concentrations were measured at regular intervals. Glucose tolerance, insulin sensitivity, novel object recognition,\n                      <jats:styled-content style=\"fixed-case\">DPP\u20104<\/jats:styled-content>\n                      activity, hormone analysis, hippocampal gene expression and histology were performed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Sitagliptin decreased circulating\n                      <jats:styled-content style=\"fixed-case\">DPP\u20104<\/jats:styled-content>\n                      activity and improved glucose tolerance, glucose\u2010stimulated insulin secretion and insulin sensitivity, and reduced plasma triglycerides and cholesterol levels.\n                      <jats:styled-content style=\"fixed-case\">DPP\u20104<\/jats:styled-content>\n                      inhibition improved recognition memory (1.2\u2010fold increase) without affecting hypermoteric activity or anxiety levels. Improvement in memory and learning was linked to reduced immunostaining for 8\u2010oxoguanine and increased doublecortin staining in the hippocampus, which were indicative of reduced brain oxidative stress and increased hippocampal neurogenesis, respectively. These effects were associated with significant upregulation of hippocampal gene expression of glucagon\u2010like peptide\u20101 (\n                      <jats:styled-content style=\"fixed-case\">GLP\u20101<\/jats:styled-content>\n                      ) receptor, glucose\u2010dependent insulinotropic polypeptide receptor, synaptophysin, sirtuin 1, glycogen synthase kinase 3\u03b2, superdioxide mutase 2, nuclear factor (erythroid\u2010derived 2)\u2010like 2 and vascular endothelial growth factor. Total plasma and brain\n                      <jats:styled-content style=\"fixed-case\">GLP\u20101<\/jats:styled-content>\n                      concentrations were significantly increased after sitagliptin therapy, whereas\n                      <jats:styled-content style=\"fixed-case\">DPP\u20104<\/jats:styled-content>\n                      activity in brain tissue was not altered.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These studies show that sitagliptin can reverse memory impairment in high\u2010fat\u2010fed mice and is also associated with improved insulin sensitivity, enhanced hippocampal neurogenesis and reduced oxidative stress.\n                      <jats:styled-content style=\"fixed-case\">DPP\u20104<\/jats:styled-content>\n                      inhibitors may therefore exhibit dual benefits by improving metabolic control and reducing the decline in cognitive function.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.12432","type":"journal-article","created":{"date-parts":[[2015,1,7]],"date-time":"2015-01-07T22:46:02Z","timestamp":1420670762000},"page":"403-413","source":"Crossref","is-referenced-by-count":126,"title":["Sitagliptin, a dipeptidyl peptidase\u20104 inhibitor, improves recognition memory, oxidative stress and hippocampal neurogenesis and upregulates key genes involved in cognitive decline"],"prefix":"10.1111","volume":"17","author":[{"given":"V. 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