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We demonstrate that neural progenitor cells (NPCs) and immature dentate granule cells (DGCs) within the adult murine hippocampus are particularly sensitive to rAAV-induced cell death. Cell loss is dose dependent and nearly complete at experimentally relevant viral titers. rAAV-induced cell death is rapid and persistent, with loss of BrdU-labeled cells within 18 hr post-injection and no evidence of recovery of adult neurogenesis at 3 months post-injection. The remaining mature DGCs appear hyperactive 4 weeks post-injection based on immediate early gene expression, consistent with previous studies investigating the effects of attenuating adult neurogenesis. In vitro application of AAV or electroporation of AAV2 inverted terminal repeats (ITRs) is sufficient to induce cell death. Efficient transduction of the dentategyrus (DG)\u2013 without ablating adult neurogenesis\u2013 can be achieved by injection of rAAV2-retro serotyped virus into CA3. rAAV2-retro results in efficient retrograde labeling of mature DGCs and permits in vivo two-photon calcium imaging of dentate activity while leaving adult neurogenesis intact. These findings expand on recent reports implicating rAAV-linked toxicity in stem cells and other cell types and suggest that future work using rAAV as an experimental tool in the DG and as a gene therapy for diseases of the central nervous system should be carefully evaluated.<\/jats:p>","DOI":"10.7554\/elife.59291","type":"journal-article","created":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T08:00:31Z","timestamp":1626249631000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.59291","source":"Crossref","is-referenced-by-count":82,"title":["AAV ablates neurogenesis in the adult murine hippocampus"],"prefix":"10.7554","volume":"10","author":[{"given":"Stephen","family":"Johnston","sequence":"first","affiliation":[{"name":"Neurosciences Graduate Program, University of California, San Diego, La Jolla, United States"},{"name":"Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah L","family":"Parylak","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacy","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, United States"},{"name":"Department of Neurosciences, University of California, San Diego, La Jolla, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nolan","family":"Mac","sequence":"additional","affiliation":[{"name":"Department of Biology, University of California, San Diego, La Jolla, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Lim","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iryna","family":"Gallina","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cooper","family":"Bloyd","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Newberry","sequence":"additional","affiliation":[{"name":"Department of Physics, University of California, San Diego, La Jolla, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian D","family":"Saavedra","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ondrej","family":"Novak","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Epileptology, Department of Physiology, Second Faculty of Medicine, Charles University, Prague, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J Tiago","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Ruth L. and David S. 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