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Insulin\u2010like growth factor 1 (IGF1) has proven to be a potent neuroprotective molecule in animal models of age\u2010related neurodegeneration. In this regard, adenoviral gene transfer aiming at IGF1 brain overexpression has been hitherto an underexplored approach for the sAD treatment. We postulated enhanced IGF1 signaling in the brain as a restorative means in the diseased brain to revert cognitive deficit and restore hippocampal function. We implemented recombinant adenovirus mediated intracerebroventricular IGF1 gene transfer on the streptozotocin (STZ) induced sAD rat model, using 3\u2010month\u2010old male Sprague Dawley rats. This approach enhanced IGF1 signaling in the hippocampus and dampened sAD phosphorylated Tau. We found a remarkable short\u2010term improvement in species\u2010typical behavior, recognition memory, spatial memory, and depressive\u2010like behavior. Histological analysis revealed a significant recovery of immature hippocampal neurons. We additionally recorded an increase in hippocampal microglial cells, which we suggest to exert anti\u2010inflammatory effects. Finally, we found decreased levels of pre\u2010 and postsynaptic proteins in the hippocampus of STZ animals. Interestingly, IGF1 gene transfer increased the levels of PSD95 and GAD65\/67 synaptic markers, indicating that the treatment enhanced the synaptic plasticity. We conclude that exogenous activation of IGF1 signaling pathway, 1 week after intracerebroventricular STZ administration, protects hippocampal immature neurons, dampens phosphorylated Tau levels, improves synaptic function and therefore performs therapeutically on the sAD STZ model. Hence, this study provides strong evidence for the use of this trophic factor to treat AD and age\u2010related neurodegeneration.<\/jats:p>","DOI":"10.1002\/hipo.23379","type":"journal-article","created":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T13:39:42Z","timestamp":1627565982000},"page":"1137-1153","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Insulin\u2010like growth factor 1 gene transfer for sporadic Alzheimer's disease: New evidence for trophic factor mediated hippocampal neuronal and synaptic recovery\u2010based behavior improvement"],"prefix":"10.1002","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8099-9421","authenticated-orcid":false,"given":"Mar\u00eda Florencia","family":"Zappa Villar","sequence":"first","affiliation":[{"name":"Institute for Biochemical Research (INIBIOLP)\u2014National Scientific and Technical Research Council (CONICET)\u2014School of Medical Sciences 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