The effect of photoperiod and high fat diet on the cognitive response in photoperiod-sensitive F344 rats

Highlights

• Diet and photoperiod have an impact on object recognition in photoperiod-sensitive F344 rats.

• Rats in long photoperiod on chow diet can perform a novel object recognition task suggesting their short-term memory remains intact.

• Our behavioral analysis suggests that high fat diet induces an impairment in memory independent of photoperiod.

• Changing rats to short photoperiod conditions impairs their ability to differentiate between normal and familiar objects independent of diet.

Abstract

In many species, seasonal changes in day length (photoperiod) have profound effects on physiology and behavior. In humans, these include cognitive function and mood. Here we investigated the effect of photoperiod and high fat diets on cognitive deficits, as measured by novel object recognition, in the photoperiod-sensitive F344 rat, which exhibits marked natural changes in growth, body weight and food intake in response to photoperiod. 32 male juvenile F344 rats were housed in either long or short photoperiod and fed either a high fat or nutrient-matched chow diet. Rats were tested in the novel object recognition test before photoperiod and diet intervention and re-tested 28 days after intervention. In both tests during the acquisition trials there was no significant difference in exploration levels of the left and right objects in the groups. Before intervention, all groups showed a significant increase in exploration of the novel object compared to the familiar object. However, following the photoperiod and diet interventions the retention trial revealed that only rats in the long photoperiod-chow group explored the novel object significantly more than the familiar object, whereas all other groups showed no significant preference. These results suggest that changing rats to short photoperiod impairs their memory regardless of diet. The cognitive performance of rats on long photoperiod-chow remained intact, whereas the high fat diet in the long photoperiod group induced a memory impairment. In conclusion, our study suggests that photoperiod and high fat diet have an impact on object recognition in photoperiod-sensitive F344 rats.

Introduction

Seasonal animals have evolved diverse seasonal variations in physiology and behavior to accommodate yearly changes in environmental and climatic conditions. These physiological and behavioral changes are initiated by changes in day length (photoperiod) and include annually occurring phenomena such as migration, hibernation, torpor and reproduction [16]. The broad importance of seasonality in physiology and biomedical research has increasingly been recognized in recent years [42]. Seasonal animals undergo pronounced cycles of weight gain and weight loss to precisely control their energy stores as part of their natural physiology. Unlocking the basis of seasonal body weight regulation is therefore important not only to our understanding of basic physiology, but to understand the long-term impact of seasonal changes on the brain, behavior and cognition in animals, including humans [17].

The neuroendocrine mechanisms underlying seasonal energy balance regulation and reproduction involve dynamic interactions across multiple central nervous system substrates and hormonal messengers to provide system-wide orchestration [21]. Seasonal changes in photoperiod are mediated through the nocturnal secretion of melatonin from the pineal gland which relays photoperiodic information to the pars tuberalis of the pituitary gland to regulate the release of thyroid-stimulating hormone (TSH). In short photoperiod (winter: short days and long nights), the increased duration of melatonin signal inhibits the release of TSH whereas in long photoperiod (summer: long days and short nights), the short duration of melatonin allows TSH release. The hypothalamus integrates the TSH signal by increasing the expression of deiodinase enzymes to catalyze the conversion of inactive thyroid hormone T4 to biological active thyroid hormone T3. Increased T3 regulates key downstream pathways, such as retinoic acid signaling, resulting in appropriate seasonal phenotypes [16, 17]. This process also involves the photoperiodic regulation of neuropeptides localized in discrete appetite-regulating centers of the hypothalamus to regulate food intake and body composition [21].

To study the interactions of the mechanisms involved in the regulation of body weight and growth with those involved in diet-induced obesity, we previously investigated the effect of photoperiod and high fat diet on physiology (body weight, body composition, food intake), circulating levels of hormones that regulate feeding status and hypothalamic gene expression in Fisher F344 rats [37]. The study showed that photoperiod and high fat diet regulate body weight and body composition through independent pathways, with photoperiod primarily effecting growth and lean mass accretion and high fat diet effecting adipose tissue accretion. Anecdotal findings from this study suggested that photoperiod and high fat diet had an effect on rats’ behavior, insofar we noticed that animals housed in long photoperiod demonstrated increased explorative behavior and seemed generally more alert (unpublished data). It is well established that high fat diet impairs cognitive function and induces cognitive deficits in rodent models [3, 7, 23, 26, 33]. Much less common are reports on the effect of photoperiod on cognitive performance, yet seasonal environmental changes are expected to influence cognition to meet the ecological needs of animals [2].

The best studied examples of seasonal changes in cognitive processes come from songbirds where seasonal changes in song production and learning are accompanied by changes in the brain regions controlling song [46]. Interestingly, a recent study has shown that these seasonal changes are not under photoperiod control [35]. Additionally, the hippocampus undergoes seasonal changes in food-storing birds and brood parasites, but similarly this seems independent of photoperiod [40]. In some seasonal breeders, such as cowbirds, deer mice and voles, spatial memory is enhanced prior to the breeding season [4, 10, 11]. Male African stripped mice show increased spatial performance and attention during winter and it has been suggested that this might be due to greater dispersal motivation before breeding season [24]. Interestingly, female stripped mice do not show the same seasonal variation [24, 25]. These studies provide compelling evidence for seasonal patterns of cognitive performance, however, studies designed to examine photoperiod control of cognition are limited.

Interestingly, in non-seasonal animals, for example the non-photoperiodic Wistar rat, there is some evidence indicating that photoperiod has an impact on animal behavior, including depression, anxiety and stress [1]. This provides an exciting opportunity for novel treatment strategies using photoperiod that may be applicable to humans. Indeed, short photoperiod has been suggested as an approach in the management of central nervous system injuries [44] and therapeutic interventions targeting photoperiodic regulated dopamine signaling could help patients suffering from seasonal affective disorders [34].

Here we investigated the effect of photoperiod and diet on cognition in the photoperiod-sensitive F344 rat. The inbred F344 rat strain is one of the few rat strains that shows pronounced photoperiod-induced changes in its metabolic phenotype, growth and reproductive status [45]. In the laboratory, a simple switch in photoperiod induces large scale changes in body composition, food intake, reproduction and hypothalamic gene expression within 2–4 weeks [[18], [19], [20], 37]. Furthermore, the F344 rat strain is one of the strains preferred in behavioral tests due to low level activation of the hypothalamic-pituitary-adrenal axis and low open field defecation [13, 15, 47]. Thus, the F344 rat is the ideal model to study photoperiod regulation of cognitive flexibility. To test photoperiod control of cognition, we used the novel object recognition (NOR) task, a spontaneous and ethologically relevant behavioral paradigm that is based on rodents’ natural tendency to explore novel stimuli and environments [8]. This is a robust, well-characterized behavioral task which is routinely used to assess cognition and natural behavior in an open field arena [5, 14, 29, 30]. In line with previous studies, we predicted that high fat diet would decrease cognitive performance in F344 rats independent of photoperiod. Given that F344 rats breed during long photoperiod [45], we hypothesized that cognitive performance would be enhanced in long photoperiod in these rats.