{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:15:02Z","timestamp":1785413702016,"version":"3.56.0"},"reference-count":55,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007086","name":"Sel\u00e7uk University","doi-asserted-by":"publisher","award":["22202016"],"award-info":[{"award-number":["22202016"]}],"id":[{"id":"10.13039\/501100007086","id-type":"DOI","asserted-by":"publisher"}]},{"award":["22202016"],"award-info":[{"award-number":["22202016"]}],"id":[{"id":"https:\/\/ror.org\/045hgzm75","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This study investigated the effects of moderate chronic exercise on hippocampal integrity, motor learning, and neuroplasticity markers in diabetic aged (16-month-old) female Wistar rats. Forty Wistar rats were divided into four groups: Control (n = 10), Exercise Control (n = 10), Diabetes (n = 10), and Diabetes + Exercise (n = 10). Diabetes was induced via streptozotocin (40 mg\/kg, i.p.), while exercise groups performed 45 min daily treadmill sessions for four weeks. Motor coordination was assessed using the rotarod test. Hippocampal Nogo-A, KLOTHO, and NZF-2b gene expressions were analyzed by RT-PCR, and oxidative stress markers (MDA, GSH) were measured by ELISA. In the diabetes group (G3), Nogo-A and MDA levels significantly increased (p &lt; 0.05), while KLOTHO, NZF-2b, and GSH levels decreased (p &lt; 0.05). Chronic exercise reversed these pathological changes by decreasing Nogo-A and MDA (p &lt; 0.05) and increasing KLOTHO, NZF-2b, and GSH (p &lt; 0.05). Behaviorally, the diabetes group (G3) showed the lowest rotarod performance (p &lt; 0.05), which significantly improved with exercise (p &lt; 0.05). Findings suggest that diabetes and aging impair neuroplasticity-related gene expression and increase oxidative stress in the hippocampus. Chronic exercise (G2 and 4) exerts neuroprotective effects by mitigating these damages. Specifically, the upregulation of NZF-2b indicates that exercise may support neuroplasticity through transcriptional regulation, offering a preventive strategy against diabetic hippocampal degeneration.<\/jats:p>","DOI":"10.3390\/ijms27146450","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T16:19:27Z","timestamp":1784564367000},"page":"6450","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Moderate Exercise Mitigates Diabetes-Induced Hippocampal Dysfunction in Aged Rats"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9752-7508","authenticated-orcid":false,"given":"Saltuk Bugra","family":"Baltaci","sequence":"first","affiliation":[{"name":"Research Institute for Health Sciences and Technologies (SABITA), Department of Physiology, Medical Faculty, Istanbul Medipol University, 34810 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0548-9098","authenticated-orcid":false,"given":"G\u00f6zde","family":"Acar","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical Faculty, Sel\u00e7uk University, 42130 Konya, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2391-2152","authenticated-orcid":false,"given":"Elif","family":"Gulbahce-Mutlu","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Medical Faculty, Konya Chamber of Commerce (KTO), Karatay University, 42020 Konya, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayyuce","family":"Kumas","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical Faculty, Sel\u00e7uk University, 42130 Konya, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5453-5463","authenticated-orcid":false,"given":"Ay\u015fenur Feyza","family":"Bayiroglu","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical Faculty, Bandirma Onyedi Eylul University, 10200 Band\u0131rma, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasim","family":"Mogulkoc","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical Faculty, Sel\u00e7uk University, 42130 Konya, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulkerim Kasim","family":"Baltaci","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical Faculty, Sel\u00e7uk University, 42130 Konya, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.2337\/dc24-0860","article-title":"Diabetes, prediabetes, and brain aging: The role of healthy lifestyle","volume":"47","author":"Dove","year":"2024","journal-title":"Diabetes Care"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.1007\/s00592-025-02583-3","article-title":"The impact of type 2 diabetes on aging: Multidimensional approaches to preserve cognitive health","volume":"62","author":"Lucia","year":"2025","journal-title":"Acta Diabetol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e775","DOI":"10.1038\/tp.2016.39","article-title":"Advanced brain aging: Relationship with epidemiologic and genetic risk factors, and overlap with Alzheimer disease atrophy patterns","volume":"6","author":"Habes","year":"2016","journal-title":"Transl. 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