Short exposure to a diet rich in both fat and sugar or sugar alone impairs place, but not object recognition memory in rats

Highlight

• In rats fed high fat/sugar diets, rapid deficits in hippocampal-dependent memory were associated with increased cytokines and oxidative stress markers.

Abstract

High energy diets have been shown to impair cognition however, the rapidity of these effects, and the dietary component/s responsible are currently unclear. We conducted two experiments in rats to examine the effects of short-term exposure to a diet rich in sugar and fat or rich in sugar on object (perirhinal-dependent) and place (hippocampal-dependent) recognition memory, and the role of inflammatory mediators in these responses. In Experiment 1, rats fed a cafeteria style diet containing chow supplemented with lard, cakes, biscuits, and a 10% sucrose solution performed worse on the place, but not the object recognition task, than chow fed control rats when tested after 5, 11, and 20 days. In Experiment 2, rats fed the cafeteria style diet either with or without sucrose and rats fed chow supplemented with sucrose also performed worse on the place, but not the object recognition task when tested after 5, 11, and 20 days. Rats fed the cafeteria diets consumed five times more energy than control rats and exhibited increased plasma leptin, insulin and triglyceride concentrations; these were not affected in the sucrose only rats. Rats exposed to sucrose exhibited both increased hippocampal inflammation (TNF-α and IL-1β mRNA) and oxidative stress, as indicated by an upregulation of NRF1 mRNA compared to control rats. In contrast, these markers were not significantly elevated in rats that received the cafeteria diet without added sucrose. Hippocampal BDNF and neuritin mRNA were similar across all groups. These results show that relatively short exposures to diets rich in both fat and sugar or rich in sugar, impair hippocampal-dependent place recognition memory prior to the emergence of weight differences, and suggest a role for oxidative stress and neuroinflammation in this impairment.

Introduction

Many people in developed countries eat a diet that is rich in saturated fat and refined sugar (Kearney, 2010). Excessive intake of this diet leads to increased body weight, progression into obesity, and the development of metabolic and cardiovascular disorders (Bruce-Keller et al., 2009, Haslam and James, 2005). Epidemiological data has also associated the consumption of high energy diets with an increased risk of age related deficits and neurological diseases including dementia and Alzheimer’s disease (Eskelinen et al., 2008, Grant et al., 2002, Solfrizzi et al., 2010). Studies with rodents have confirmed that the long-term intake of such a diet produces cognitive deficits, especially in spatial tasks that require the hippocampus (Heyward et al., 2012, McNay et al., 2010, Ross et al., 2009). Some of these studies have also identified changes in the hippocampus that may mediate the link between obesity and cognitive deficits. Such changes include oxidative stress, neuroinflammation, as well as decreased levels of neurotrophins (Molteni et al., 2004, Pistell et al., 2010).

Moreover there is very recent evidence that cognitive deficits can not only be produced by long-term excessive intake of a high energy diet but also by relative short exposures to such a diet. Holloway et al. (2011) reported that healthy adults who ate a high fat diet for 5 days performed worse on tasks measuring attention and speed of retrieval than they had prior to the diet. Kanoski and Davidson (2010) also found that rats exposed to a high fat and glucose diet performed worse on a spatial task than chow fed control rats after only 3 days whereas 30 days exposure was necessary for non-spatial memory impairments.

The present experiments constituted a further study of the effects of relatively short-term exposure to a high energy diet on cognition in rats. We set out to confirm and extend previous reports that the consumption of diets high in both fat and sugar is accompanied by impaired memory retention. The modern diet is replete with a diverse range of foods that are rich in fat and sugar and for this reason in the first experiment we chose a cafeteria style diet (cakes, biscuits, lard) supplemented with a 10% sucrose solution. To compare non-spatial and spatial memory we employed the object and place recognition tasks, which are respectively dependent on the perirhinal cortex and the hippocampus (Aggleton and Brown, 2005). We assessed performance on both tasks from 5 to 21 days diet exposure to examine changes in the magnitude of specific deficits. There is some evidence that the hippocampus is particularly sensitive to changes in dietary intake and impairments have been reported on hippocampal-dependent tasks prior to substantial weight gain (Kanoski and Davidson, 2010, Murray et al., 2009). Here we specifically aimed to test short, rather than the more commonly studied long term dietary interventions (3–12 months).

To assess the relative contributions of fat and sugar to the behavioral effects observed, our second experiment included two additional diet groups, a regular diet supplemented with 10% sucrose and the cafeteria style diet without sucrose. At the end of the study we assessed plasma leptin, insulin and triglycerides as well as hippocampal expression of inflammatory markers; tumor necrosis factor (TNF-α) and interleukin 1 (IL-1β), oxidative stress markers; nuclear respiratory factor 1 (NRF1), and sirtuin 3 (SIRT3), as well as brain-derived neurotrophic factor (BDNF) and neuritin. These markers were selected as CNS inflammation has been reported after as little as 1–3 days on a high energy diet (Hansen et al., 1998, Thaler et al., 2012) and obesity itself is characterized by a state of low grade, chronic inflammation (Bastard et al., 2006). In addition, oxidative stress is believed to be one of the first events following the consumption of a high energy diet and it may be responsible for the decreased levels of BDNF reported in long term diet studies (Molteni et al., 2004). NRF1 is involved in the activation of antioxidant response element-dependent genes (Ohtsuji et al., 2008) while SIRT3 has roles in metabolism, oxidative stress and cell survival (Weir et al., 2013). BDNF has been implicated in a number of processes postulated to underlie hippocampal-dependent learning and memory including long term potentiation, neurogenesis and synaptic plasticity (Stranahan et al., 2008, Yamada et al., 2002).