Paulo, Sara LMiranda-Lourenço, CatarinaBelo, Rita F.Rodrigues, Rui S.Fonseca-Gomes, JoãoTanqueiro, SaraGeraldes, VeraRocha, IsabelSebastião, Ana MXapelli, SaraDiógenes, Maria José2022-01-042022-01-042021Curr Issues Mol Biol. 2021 Dec 18;43(3):2305-23191467-3037http://hdl.handle.net/10451/50686© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).The increasing consumption of sugar and fat seen over the last decades and the consequent overweight and obesity, were recently linked with a deleterious effect on cognition and synaptic function. A major question, which remains to be clarified, is whether obesity in the elderly is an additional risk factor for cognitive impairment. We aimed at unravelling the impact of a chronic high caloric diet (HCD) on memory performance and synaptic plasticity in aged rats. Male rats were kept on an HCD or a standard diet (control) from 1 to 24 months of age. The results showed that under an HCD, aged rats were obese and displayed significant long-term recognition memory impairment when compared to age-matched controls. Ex vivo synaptic plasticity recorded from hippocampal slices from HCD-fed aged rats revealed a reduction in the magnitude of long-term potentiation, accompanied by a decrease in the levels of the brain-derived neurotrophic factor receptors TrkB full-length (TrkB-FL). No alterations in neurogenesis were observed, as quantified by the density of immature doublecortin-positive neurons in the hippocampal dentate gyrus. This study highlights that obesity induced by a chronic HCD exacerbates age-associated cognitive decline, likely due to impaired synaptic plasticity, which might be associated with deficits in TrkB-FL signaling.engAgingBrain-derived neurotrophic factor (BDNF)High caloric dietHippocampal plasticityMemoryNeurogenesisObesityjournal article10.3390/cimb430301621467-3045