{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:25:02Z","timestamp":1787030702327,"version":"build-2736575974"},"reference-count":36,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T00:00:00Z","timestamp":1786838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["52077057"],"award-info":[{"award-number":["52077057"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["52077057"],"award-info":[{"award-number":["52077057"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003787","name":"Hebei Natural Science Foundation","doi-asserted-by":"crossref","award":["F2025202066"],"award-info":[{"award-number":["F2025202066"]}],"id":[{"id":"10.13039\/501100003787","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sci.","Brain Sciences"],"abstract":"<jats:p>Background\/Objectives: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulatory approach with potential therapeutic value for cognitive impairment in Alzheimer\u2019s disease (AD). Ferroptosis-related oxidative injury has been implicated in AD-associated neuronal dysfunction, but whether rTMS-induced functional improvement is accompanied by changes in ferroptosis-related oxidative injury remains unclear. This study evaluated the effects of high-frequency rTMS on cognitive function, hippocampal neuronal excitability, and ferroptosis-related oxidative injury in amyloid precursor protein\/presenilin-1 (APP\/PS1) mice, using Ferrostatin-1 (Fer-1) as a pharmacological comparator. Methods: Six-month-old female mice were used, including age-matched C57BL\/6J controls and APP\/PS1 mice assigned to the AD + Sham, AD + rTMS, and AD + Fer-1 groups (n = 6 per group). After 14 days of intervention, cognitive performance was assessed using behavioral tests. Whole-cell patch-clamp recordings were performed in hippocampal dentate gyrus granule neurons to evaluate neuronal excitability and voltage-gated sodium (Na+) and potassium (K+) channel properties. Biochemical assays and transmission electron microscopy were used to assess oxidative, iron-related, and mitochondrial changes, and mitochondrial ultrastructure was examined in an independent cohort (n = 3 per group) using transmission electron microscopy. Results: Compared with AD + Sham mice, high-frequency rTMS improved cognitive performance, increased evoked action potential firing, lowered the elevated action potential threshold, partially restored voltage-gated Na+ and K+ current amplitudes, and accelerated recovery of Na+ currents from inactivation. Fer-1 produced partially overlapping, but not identical, effects across behavioral, electrophysiological, biochemical, and ultrastructural outcomes. Both interventions increased hippocampal glutathione (GSH) levels, reduced malondialdehyde (MDA) and total iron levels, partially restored superoxide dismutase (SOD) activity, and improved mitochondrial ultrastructure and reduced the prevalence of mitochondrial profiles with small cross-sectional areas. Conclusions: High-frequency rTMS improved cognitive and hippocampal neuronal outcomes in female APP\/PS1 mice. These improvements were accompanied by biochemical and mitochondrial changes compatible with attenuation of ferroptosis-related injury. However, the findings do not establish ferroptosis inhibition as either necessary or sufficient for the effects of rTMS.<\/jats:p>","DOI":"10.3390\/brainsci16080868","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T13:42:17Z","timestamp":1786974137000},"page":"868","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["High-Frequency rTMS Improves Cognitive Deficits in APP\/PS1 Mice with Attenuation of Ferroptosis-Related Oxidative Injury"],"prefix":"10.3390","volume":"16","author":[{"given":"Boya","family":"Lu","sequence":"first","affiliation":[{"name":"College of Health Sciences & Biomedical Engineering, Hebei University of Technology, Tianjin 300130, China"},{"name":"State Key Laboratory of Intelligent Power Distribution Equipment and System, Tianjin 300130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Health Sciences & Biomedical Engineering, Hebei University of Technology, Tianjin 300130, China"},{"name":"State Key Laboratory of Intelligent Power Distribution Equipment and System, Tianjin 300130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8825-090X","authenticated-orcid":false,"given":"Zihao","family":"Ren","sequence":"additional","affiliation":[{"name":"College of Health Sciences & Biomedical Engineering, Hebei University of Technology, Tianjin 300130, China"},{"name":"State Key Laboratory of Intelligent Power Distribution Equipment and System, Tianjin 300130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianjiu","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Health Sciences & Biomedical Engineering, Hebei University of Technology, Tianjin 300130, China"},{"name":"State Key Laboratory of Intelligent Power Distribution Equipment and System, Tianjin 300130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixuan","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Health Sciences & Biomedical Engineering, Hebei University of Technology, Tianjin 300130, China"},{"name":"State Key Laboratory of Intelligent Power Distribution Equipment and System, Tianjin 300130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Ding","sequence":"additional","affiliation":[{"name":"College of Health Sciences & Biomedical Engineering, Hebei University of Technology, Tianjin 300130, China"},{"name":"State Key Laboratory of Intelligent Power Distribution Equipment and System, Tianjin 300130, China"},{"name":"Hebei Key Laboratory of Bioelectromagnetics and Neural Engineering, Tianjin 300130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"102481","DOI":"10.1016\/j.arr.2024.102481","article-title":"Pathogenesis, diagnostics, and therapeutics for Alzheimer\u2019s disease: Breaking the memory barrier","volume":"101","author":"Kamatham","year":"2024","journal-title":"Ageing Res. 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