High Caloric Diet Induces Memory Impairment and Disrupts Synaptic Plasticity in Aged Rats

Abstract

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.

Effects of High-Fat and High-Fat High-Sugar Diets in the Anxiety, Learning and Memory, and in the Hippocampus Neurogenesis and Neuroinflammation of Aged Rats

“…Furthermore, the impairment observed throughout the acquisition phase had consequences in the spatial memory evaluated in the probe trial on day 15, as shown by the lower platform crossings of the HFHS animals and by the fact that HFHS animals spent less time in the target quadrant than HF and control animals. Reinforcing the information regarding the deleterious impact of HFHS on cognition, we also found a significant impairment of the working memory process in HFHS-aged animals, corroborating previous studies using high-caloric diets in middle-aged rats [ 12 , 17 , 39 ]. Interestingly, relative to the HF diet, we found that our HF diet did not significantly impair spatial learning processes but was indeed able to impair spatial memory and working memory.…”

Nutrition and adult neurogenesis in the hippocampus: Does what you eat help you remember?

“…Learning and memory, closely related to AHN, can be influenced by diet during development and into adulthood; there is an inverse correlation between the quality of the diet and the disorders associated with these hippocampal abilities (Zainuddin and Thuret, 2012;Murphy et al, 2014). In this context, highcalorie diets (HCD), characterized in rodents by high levels of saturated fats (40-60% fat) and/or refined sugars for at least 4 weeks, strongly impairs in a sex specific manner AHN decreasing proliferating cells, differentiated neuroblasts/immature neurons and mature neurons; and has been associated with disfunctions in hippocampal-dependent memory and neuroinflammation, (Park et al, 2010;van der Borght et al, 2011;Hsu et al, 2015;Pérez-Garciá et al, 2016;Robison et al, 2020;Kim et al, 2021;Paulo et al, 2021;Fierros-Campuzano et al, 2022). Most of these studies affirm that the downregulation of the neurotrophin BDNF and its signaling through cAMP response element-binding (CREB) and TrkB as the main mechanism involved in HCD-induced AHN injury (Molteni et al, 2002;Hwang et al, 2008;White et al, 2009;Kim et al, 2021;Paulo et al, 2021).…”

Feeding the Brain: Effect of Nutrients on Cognition, Synaptic Function, and AMPA Receptors

“…This stimulation increases the number of CP-AMPARs (GluA1-GluA1 tetramers) in the PSZ, inducing trafficking to the cell surface via the recycling pathway and lateral movement from perisynaptic sites, and enhancing synaptic transmission efficiency. It has been reported that long-term WD-impaired synaptic plasticity in the hippocampus (HPC) reduces dendritic spine density and LTP [ 54 , 55 , 64 ], and also that the WD alters dendritic arborization, which is reduced in the HPC and increased in the entorhinal cortex [ 45 ]. This last finding could be a compensatory effect due to synaptic loss in distal regions like the HPC or even in proximal synapses, since the WD has also been reported to impair episodic memory in this particular case.…”

“…Levels of the main neurotrophin, i.e., brain-derived neurotrophic factor (BDNF), were reduced in the HPC of adult mice after long-term exposure (2–8 months) to the WD [ 47 , 54 , 63 , 64 , 66 , 70 ], while no differences were observed for shorter exposure (20–42 days) [ 46 , 49 , 51 ]. A decrease in the BDNF receptor, tropomyosin receptor kinase B (TrkB), has also been reported [ 55 , 59 ]. Interestingly, not all nutritional sources alter BDNF levels in the same way.…”