Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.
Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.
Curr Issues Mol Biol. 2021 Dec 18;43(3):2305-2319. doi: 10.3390/cimb43030162.
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.
过去几十年,糖和脂肪的摄入量不断增加,导致超重和肥胖,最近与认知和突触功能的不良影响有关。一个悬而未决的主要问题是,老年人肥胖是否是认知障碍的另一个危险因素。我们旨在揭示慢性高热量饮食(HCD)对老年大鼠记忆表现和突触可塑性的影响。雄性大鼠从 1 到 24 个月大时,分别喂食 HCD 或标准饮食(对照)。结果表明,在 HCD 下,老年大鼠肥胖,并表现出与年龄匹配的对照组相比,明显的长期识别记忆障碍。从 HCD 喂养的老年大鼠的海马切片中记录的离体突触可塑性显示,长时程增强的幅度降低,同时脑源性神经营养因子受体 TrkB 全长(TrkB-FL)水平降低。通过海马齿状回中不成熟的双皮质素阳性神经元的密度来量化,未观察到神经发生的改变。这项研究强调,慢性 HCD 引起的肥胖会加剧与年龄相关的认知能力下降,可能是由于突触可塑性受损所致,这可能与 TrkB-FL 信号转导缺陷有关。