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Although AHN declines during aging and is impaired in Alzheimer's disease (AD), the cell\u2010type\u2010specific alterations within the DG underlying this decline remain poorly characterized. Given the critical role of glycogen synthase kinase\u20103\u03b2 (GSK\u20103\u03b2) in AD pathogenesis and AHN regulation, we studied how the overexpression of this kinase in dentate granule cells (DGCs) remodels the cellular and vascular composition of the DG throughout life. Using a layer\u2010resolved approach (SGZ vs. granule cell layer (GCL)) and mice of distinct ages (4\u201330\u2009months), we quantified glial densities, cellular contacts, vascular architecture, and cytokine profiles in wild\u2010type (WT) and GSK\u20103\u03b2\u2010overexpressing (GSK\u20103\u03b2\u2010OE) mice. In the former, aging was associated with a layer\u2010specific reorganization, characterized by progressive astrocyte loss in the SGZ, midlife increases in GCL microglia, a reduction in oligodendroglial progenitors, and enhanced SGZ vascularization. GSK\u20103\u03b2 overexpression accelerated age\u2010related changes, triggering premature SGZ astrocyte depletion by 4\u2009months, broader disruption featuring reduced SGZ microglial and mature oligodendrocyte densities accompanied by increased microglial morphological complexity, vascular restructuring, and a shift toward a pro\u2010inflammatory environment. Therefore, neuronal GSK\u20103\u03b2 overexpression promoted a non\u2010cell\u2010autonomous reorganization of the DG, consistent with premature remodeling of the neurogenic niche. These results provide mechanistic insights into AHN failure in AD and point to the modulation of GSK\u20103\u03b2 activity as a strategy to preserve DG integrity.<\/jats:p>","DOI":"10.1002\/glia.70248","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T05:39:52Z","timestamp":1792474792000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuronal Overexpression of Glycogen Synthase Kinase\u20103\u03b2 Accelerates Age\u2010Related Glial, Vascular, and Inflammatory Remodeling of the Murine Dentate Gyrus"],"prefix":"10.1002","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7977-1964","authenticated-orcid":false,"given":"Ana V.","family":"Pr\u00e1danos\u2010Sen\u00e9n","sequence":"first","affiliation":[{"name":"Department of Molecular Neuropathology Centro de Biolog\u00eda Molecular \u201cSevero Ochoa\u201d (CBMSO), Spanish Research Council (CSIC)\u2013Universidad 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