Western diet and its effect on motivation, learning and memory
Creators: name: Nguyen, Jason
Publisher: name: RMIT University
Year: 2024
Subjects: classificationCode: 320903
subject: Central nervous system

description: In Western society, the prevalence of a hyper-caloric diet consisting of a high consumption of fat and simple sugars has coincided with an exponential rise in diabetes as well as cardiovascular diseases and several types of cancer. While some of these medical comorbidities are themselves associated with adverse cognitive effects, recent studies have also linked the western diet to an increased incidence of Alzheimer’s disease and mild cognitive impairment. Moreover, these disorders are considered to be major risk factors for dementia indicating that these metabolic effects have both peripheral and central effects.<br><br>Rats that have been a fed high fat diet (HFD) have shown indications to be cognitively impaired compared to those fed a normal chow diet. Research suggests that HFD consumption has a deleterious effect on spatial learning and memory, and this effect consequently may be mediated by damage to the hippocampus. To date however, there is conflicting results regarding the motivational and other types of learning implications after HFD consumption. The primary animal model of obesity used in this thesis is the western diet (WD) model of obesity in rats. This model mimics the ‘western’ diet typically consumed in developed ‘western’ countries by feeding rats a WD chow (containing 22% w/w fat) or a control chow diet (containing 6% w/w fat).<br><br>Using this model, we explored the ability of 8 weeks of WD consumption to influence changes to Pavlovian &amp; instrumental conditioning as well as motivation. This study used well characterised tests to assess whether learnt feeding behaviour can be affected by WD consumption. The ability for WD consumption to alter motivational drive in varying states of food deprivation was also investigated. Results from this study found that rats fed a WD for 8 weeks did not affect Pavlovian conditioning or motivational state. The effect of WD consumption on instrumental conditioning is still indeterminate with conflicting results. There was no change in instrumental conditioning in rats fed a WD. However, WD fed rats were impaired in progressive ratio instrumental conditioning acquisition. Additionally, WD exposed rats were no different to changes in states of food deprivation compared to control diet counterparts.<br><br>A further study investigated whether a period of 12 weeks WD consumption can affect spatial working and reference memory. No changes in spatial working or reference memory were observed in WD rats. Due to the assumed role of c-Fos, an immediate-early gene and corresponding protein, in learning and use as a surrogate marker of neuronal activation, neuronal activation in selected brain regions was evaluated. We demonstrated that WD consumption increased neuronal activation after environmental novelty in the striatum. Other brain regions involved in memory and learning were also investigated with no differences in neuronal activation before and after environmental novelty between control and WD animals.<br><br>In a series of experiments, we explored the ability of WD consumption to influence change in neurotransmitters involved in memory and learning. The expression of serotonin (5-HT) receptors 5-HT2A, 5-HT2C and the 5-HT transporter within the striatum was also investigated, as previous studies have shown that serotonin is implicated in feeding behaviour following WD consumption. Both 5-HT2C receptor and 5-HT transporter expression were found to be increased in WD rats. In contrast, 5-HT2A receptor expression was unchanged in the striatum. This suggests that WD consumption has a selective capacity to alter the serotoninergic system. Furthermore due to the well-recognised role of dopamine in cognition, including motivation, reward, punishment and working memory, the modification of dopamine metabolism was evaluated. High performance liquid chromatography analysis found reduced levels of striatal dopamine, with alterations in dopamine metabolism and turnover also evident in the hippocampus after WD consumption. These neurotransmitter changes were also observed to be independent of any change in cognitive ability. This suggests that WD consumption may instigate dopaminergic and serotoninergic adaptations before cognitive impairment transpire.<br><br>The early life nutritional environment was also investigated to ascertain if early life obesity may contribute to cognitive impairment using a neonatal overfeeding rat model of obesity. As early life is a critical window of vulnerability to long-term programming of health, cognitive assessment was performed by utilizing spatial memory function in the Y-maze test and also spatial reference and working memory using the delayed win-shift task (DWSh) in the radial arm maze. Neonatally overfed rats took longer to learn the DWSh task indicating a poorer memory acquisition compared to control. No change of spatial memory in the less cognitively demanding Y-maze test was observed in neonatally overfed rats.<br><br>The potential of a synergistic effect of WD consumption in the APPswe/PS1dE9 double transgenic Alzheimer’s mice model (APDE9) animal model memory and anxiety-like behaviour was assessed. Metabolically, this study identified that APDE9 mice fed a WD showed impaired glucose tolerance but not in wild-type WD mice or ADPE9 mice fed the control diet indicating impaired insulin receptor signalling. Both APDE9 mice fed control or WD showed a spatial memory deficit in the Y-maze when compared to their wild-type counterparts. There was no observed synergistic effect of WD consumption and APDE9 phenotype in the Y-maze. Additionally no change in anxiety-like behaviour was discerned using the open field test and the light/dark preference test.<br><br>Findings from this thesis indicate that WD consumption alone does not affect cognition using a variety of behavioural tasks. Whilst central changes in the dopaminergic and serotoninergic system ensue following WD consumption however, whether these changes occur before cognitive impairment is still unclear. The time period in which the obese phenotype transpires appears to play a factor in cognitive impairment as shown by the results in the neonatal overfeeding study. Additionally we demonstrated that WD consumption does not affect spatial memory but a possible synergistic interplay between the APDE9 mice phenotype and WD consumption may have a deleterious effect of spatial memory. Further work is necessary to elucidate the factors that contribute to the onset of cognitive impairment observed in rat models of obesity.