Pereda Pérez, InmaculadaValencia, A.Núñez, A.Sanz García, A.Baliyan, S.Zamora, B.Rodríguez Fernández, R.Esteban, J. A.Venero, C.2019-04-222019-04-2220190197-4580http://hdl.handle.net/10641/1621Social isolation predominantly occurs in elderly people and it is strongly associated with cognitive decline. However, the mechanisms that produce isolation-related cognitive dysfunction during aging remain unclear. Here, we evaluated the cognitive, electrophysiological, and morphological effects of short- (4 weeks) and long-term (12 weeks) social isolation in aged male Wistar rats. Long-term but not short-term social isolation increased the plasma corticosterone levels and impaired spatial memory in the Morris water maze. Moreover, isolated animals displayed dampened hippocampal long-term potentiation in vivo, both in the dentate gyrus (DG) and CA1, as well as a specific reduction in the volume of the stratum oriens and spine density in CA1. Interestingly, social isolation induced a transient increase in hippocampal basic fibroblast growth factor (FGF2), whereas fibroblast growth factor receptor 1 (FGFR1) levels only increased after long-term isolation. Importantly, subchronic systemic administration of FGL, a synthetic peptide that activates FGFR1, rescued spatial memory in long-term isolated rats. These findings provide new insights into the neurobiological mechanisms underlying the detrimental effects on memory of chronic social isolation in the aged.engAtribución-NoComercial-SinDerivadas 3.0 Españahttp://creativecommons.org/licenses/by-nc-nd/3.0/es/CognitionCorticosteroneHippocampusStressjournal articleopen access10.1016/j.neurobiolaging.2019.02.011