{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:55:33Z","timestamp":1791266133845,"version":"4.1.0"},"reference-count":128,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Alzheimer\u2019s Disease (AD) is a neurodegenerative disease characterized by amyloid plaque deposition, tau hyperphosphorylation, neuroinflammation, and cognitive decline. Our previous studies demonstrated that combined treatment with stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) reduces AD pathology in APP\/PS1 mice. The present study aimed to explore the molecular mechanisms underlying the effects of SCF+G-CSF using transcriptomic analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Aged APP\/PS1 mice received daily subcutaneous injections of SCF+G-CSF or vehicle for 12 days. RNA was extracted from brain tissue on day 13 for gene-chip analysis. Age-matched wild-type (WT) mice served as controls. Data were analyzed using TAC, STRING v12.0, Reactome, and ShinyGO 0.77. A total of 45,037 genes were analyzed. Twenty-seven differentially expressed genes (DEGs) met a \u2265 2-fold threshold in SCF+G-CSF-treated versus vehicle-treated APP\/PS1 mice, whereas 89 DEGs met this threshold in APP\/PS1 versus WT mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      SCF+G-CSF treatment upregulated immune-related genes, including\n                      <jats:italic>S100a8, S100a9, Ngp, Lcn2, Ltf<\/jats:italic>\n                      , and\n                      <jats:italic>Camp<\/jats:italic>\n                      , which are associated with immune regulation and amyloid-related processes. Pathway analysis identified downregulation of IL-2, IL-4, IL-7, and EGFR1 signaling and enrichment of IL-17 signaling, suggesting modulation of both innate and adaptive immune responses. SCF+G-CSF also downregulated several genes with known oncogenic functions, including\n                      <jats:italic>Cbl, Akap9, Kcnq1ot1<\/jats:italic>\n                      , and\n                      <jats:italic>Snhg11<\/jats:italic>\n                      , suggesting a potential molecular overlap between cancer- and AD-related pathways. In addition, pathway enrichment analysis identified NADPH oxidase activation through Rho GTPase signaling and greater than 400-fold enrichment of metal ion sequestration pathways following SCF+G-CSF treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>SCF+G-CSF treatment was associated with broad transcriptional changes involving immune regulation, metal ion homeostasis, and genes with known oncogenic functions. These findings provide new insights into the molecular pathways influenced by SCF+G-CSF in aged APP\/PS1 mice and identify candidate mechanisms and therapeutic targets for future investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2026.1705436","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:21:42Z","timestamp":1791264102000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Transcriptomic analysis identifies candidate molecular mechanisms underlying SCF+G-CSF-reduced neuropathology in aged APP\/PS1 mice"],"prefix":"10.3389","volume":"18","author":[{"given":"Afua","family":"Addo","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Norton College of Medicine, SUNY Upstate Medical University","place":["Syracuse, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Louisiana State University Health Sciences Center","place":["Shreveport, LA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sasidhar","family":"Murikinati","sequence":"additional","affiliation":[{"name":"Department of Neurology, Louisiana State University Health Sciences Center","place":["Shreveport, LA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Gardner","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Norton College of Medicine, SUNY Upstate Medical University","place":["Syracuse, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Ru","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Norton College of Medicine, SUNY Upstate Medical University","place":["Syracuse, NY, United States"]},{"name":"Department of Neurology, Louisiana State University Health Sciences Center","place":["Shreveport, LA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1515\/nipt-2023-0015","article-title":"Immune senescence in aged APP\/PS1 mice.","volume":"2","author":"Abdelmoaty","year":"2023","journal-title":"NeuroImmune Pharm. 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