{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:03:32Z","timestamp":1792033412070,"version":"4.4.0"},"reference-count":77,"publisher":"National Academy of Sciences","issue":"49","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,12,6]]},"abstract":"<jats:p>The adult hippocampus plays a central role in memory formation, synaptic plasticity, and neurogenesis. The subgranular zone of the dentate gyrus contains neural progenitor cells with self-renewal and multilineage potency. Transgene expression of familial Alzheimer's disease-linked mutants of \u03b2-amyloid precursor protein (APP) and presenilin-1 leads to a significant inhibition of neurogenesis, which is potentially linked to age-dependent memory loss. To investigate the effect of neurogenesis on cognitive function in a relevant disease model, FGF2 gene is delivered bilaterally to the hippocampi of APP+presenilin-1 bigenic mice via an adenoassociated virus serotype 2\/1 hybrid (AAV2\/1-FGF2). Animals injected with AAV2\/1-FGF2 at a pre- or postsymptomatic stage show significantly improved spatial learning in the radial arm water maze test. A neuropathological investigation demonstrates that AAV2\/1-FGF2 injection enhances the number of doublecortin, BrdU\/NeuN, and c-fos\u2013positive cells in the dentate gyrus, and the clearance of fibrillar amyloid-\u03b2 peptide (A\u03b2) in the hippocampus. AAV2\/1-FGF2 injection also enhances long-term potentiation in another APP mouse model (J20) compared with control AAV2\/1-GFP\u2013injected littermates. An in vitro study confirmed the enhanced neurogenesis of mouse neural stem cells by direct AAV2\/1-FGF2 infection in an A\u03b2 oligomer-sensitive manner. Further, FGF2 enhances A\u03b2 phagocytosis in primary cultured microglia, and reduces A\u03b2 production from primary cultured neurons after AAV2\/1-FGF2 infection. Thus, our data indicate that virus-mediated FGF2 gene delivery has potential as an alternative therapy of Alzheimer's disease and possibly other neurocognitive disorders.<\/jats:p>","DOI":"10.1073\/pnas.1102349108","type":"journal-article","created":{"date-parts":[[2011,11,1]],"date-time":"2011-11-01T00:21:08Z","timestamp":1320106868000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":132,"title":["FGF2 gene transfer restores hippocampal functions in mouse models of Alzheimer's disease and has therapeutic implications for neurocognitive disorders"],"prefix":"10.1073","volume":"108","author":[{"given":"Tomomi","family":"Kiyota","sequence":"first","affiliation":[{"name":"Departments of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlin L.","family":"Ingraham","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular NeuroTherapeutics, Departments of Pharmacology and Experimental Therapeutics and Neurology, and Alzheimer's Disease Center, Boston University School of Medicine, Boston, MA 02118"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T.","family":"Jacobsen","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198; 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