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In this study, the effects of ed\u2010NGF<\/jats:styled-content> on BDNF<\/jats:styled-content> signaling in the prefrontal cortex (PFC<\/jats:styled-content>) were explored in healthy and STZ<\/jats:styled-content>\u2010diabetic rats, in which cortical neuronal and axonal loss, and altered circulating BDNF<\/jats:styled-content> associated with depressive phenotype are also described.<\/jats:p><\/jats:sec>Methods<\/jats:title>STZ<\/jats:styled-content> and healthy (CTR<\/jats:styled-content>) adult rats received ed\u2010NGF<\/jats:styled-content> twice a day for 2 weeks. Depressive phenotype was identified by force swimming test (FST<\/jats:styled-content>). Proteins extracted from PFC<\/jats:styled-content> were processed for ELISA<\/jats:styled-content> and Western blot analyses to measure the expression of BDNF<\/jats:styled-content>, proBDNF<\/jats:styled-content>, and their receptors and intracellular signals.<\/jats:p><\/jats:sec>Results<\/jats:title>ed\u2010NGF<\/jats:styled-content> treatment modulates BDNF<\/jats:styled-content> pathway in PFC<\/jats:styled-content> and normalizes the STZ<\/jats:styled-content>\u2010induced BDNF<\/jats:styled-content> alterations by stimulating TRK<\/jats:styled-content>\u2010mediated survival mechanism. A decreased latency in FST<\/jats:styled-content> was also found in STZ<\/jats:styled-content> rats, while no change was observed comparing CTR<\/jats:styled-content> + NGF<\/jats:styled-content> and STZ<\/jats:styled-content> + NGF<\/jats:styled-content> with CTR<\/jats:styled-content>.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>The present data confirm the capacity of ed\u2010NGF<\/jats:styled-content> treatment to affect brain neurons and lead to brain damage recovery by activating protective and remodeling pathways triggered by BDNF<\/jats:styled-content>. We suggest that the ed\u2010NGF<\/jats:styled-content>\u2010induced changes in BDNF<\/jats:styled-content> signaling might influence the manifestation of depressive phenotype in diabetic rats.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.12661","type":"journal-article","created":{"date-parts":[[2017,1,3]],"date-time":"2017-01-03T09:26:39Z","timestamp":1483435599000},"page":"198-208","source":"Crossref","is-referenced-by-count":19,"title":["Ocular Nerve Growth Factor Administration Modulates Brain\u2010derived Neurotrophic Factor Signaling in Prefrontal Cortex of Healthy and Diabetic Rats"],"prefix":"10.1111","volume":"23","author":[{"given":"Pamela","family":"Rosso","sequence":"first","affiliation":[{"name":"National Research Council (CNR) Institute of Cell Biology & Neurobiology Rome Italy"},{"name":"Department of Science LIME University Roma Tre Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"De 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