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dc.contributor.authorDow, Antonia L.en_US
dc.contributor.authorLin, Tiffany V.en_US
dc.contributor.authorChartoff, Elena H.en_US
dc.contributor.authorPotter, Daviden_US
dc.contributor.authorMcPhie, Donna L.en_US
dc.contributor.authorVan’t Veer, Ashlee V.en_US
dc.contributor.authorKnoll, Allison T.en_US
dc.contributor.authorLee, Kristen N.en_US
dc.contributor.authorNeve, Rachael L.en_US
dc.contributor.authorPatel, Tarun B.en_US
dc.contributor.authorOngur, Dosten_US
dc.contributor.authorCohen, Bruce M.en_US
dc.contributor.authorCarlezon, William A.en_US
dc.date.accessioned2015-05-04T15:27:22Z
dc.date.issued2015en_US
dc.identifier.citationDow, A. L., T. V. Lin, E. H. Chartoff, D. Potter, D. L. McPhie, A. V. Van’t Veer, A. T. Knoll, et al. 2015. “Sprouty2 in the Dorsal Hippocampus Regulates Neurogenesis and Stress Responsiveness in Rats.” PLoS ONE 10 (3): e0120693. doi:10.1371/journal.pone.0120693. http://dx.doi.org/10.1371/journal.pone.0120693.en
dc.identifier.issn1932-6203en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:15034921
dc.description.abstractBoth the development and relief of stress-related psychiatric conditions such as major depression (MD) and post-traumatic stress disorder (PTSD) have been linked to neuroplastic changes in the brain. One such change involves the birth of new neurons (neurogenesis), which occurs throughout adulthood within discrete areas of the mammalian brain, including the dorsal hippocampus (HIP). Stress can trigger MD and PTSD in humans, and there is considerable evidence that it can decrease HIP neurogenesis in laboratory animals. In contrast, antidepressant treatments increase HIP neurogenesis, and their efficacy is eliminated by ablation of this process. These findings have led to the working hypothesis that HIP neurogenesis serves as a biomarker of neuroplasticity and stress resistance. Here we report that local alterations in the expression of Sprouty2 (SPRY2), an intracellular inhibitor of growth factor function, produces profound effects on both HIP neurogenesis and behaviors that reflect sensitivity to stressors. Viral vector-mediated disruption of endogenous Sprouty2 function (via a dominant negative construct) within the dorsal HIP of adult rats stimulates neurogenesis and produces signs of stress resilience including enhanced extinction of conditioned fear. Conversely, viral vector-mediated elevation of SPRY2 expression intensifies the behavioral consequences of stress. Studies of these manipulations in HIP primary cultures indicate that SPRY2 negatively regulates fibroblast growth factor-2 (FGF2), which has been previously shown to produce antidepressant- and anxiolytic-like effects via actions in the HIP. Our findings strengthen the relationship between HIP plasticity and stress responsiveness, and identify a specific intracellular pathway that could be targeted to study and treat stress-related disorders.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.pone.0120693en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378921/pdf/en
dash.licenseLAAen_US
dc.titleSprouty2 in the Dorsal Hippocampus Regulates Neurogenesis and Stress Responsiveness in Ratsen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS ONEen
dash.depositing.authorChartoff, Elena H.en_US
dc.date.available2015-05-04T15:27:22Z
dc.identifier.doi10.1371/journal.pone.0120693*
dash.authorsorderedfalse
dash.contributor.affiliatedChartoff, Elena
dash.contributor.affiliatedPotter, David
dash.contributor.affiliatedCarlezon, William
dash.contributor.affiliatedCohen, Bruce
dash.contributor.affiliatedMcPhie, Donna
dash.contributor.affiliatedOngur, Dost


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