Rapid and reversible impairment of episodic memory by a high-fat diet in mice

Fiona H Mclean,Christine Grant,Graham W Horgan,Fiona M Campbell,Lynda M Williams,Rosamund F Langston,Alex J Polanski,Kevin Allan,Amanda C Morris

doi:10.1038/s41598-018-30265-4

Abstract

Alzheimer’s disease is a leading cause of morbidity and mortality with no cure and only limited treatment available. Obesity and type 2 diabetes are positively associated with the development of premature cognitive decline and Alzheimer’s disease, linking diet with these conditions. Here we demonstrate that in mice episodic memory, together with spatial and contextual associative memory, is compromised after only one day of high-fat diet. However, object memory remains intact. This shows not only a more rapid effect than previously reported but also that more complex memories are at higher risk of being compromised by a high-fat diet. In addition, we show that these memory deficits are rapidly reversed by switching mice from a high-fat diet back to a low-fat diet. These findings have important implications for the contribution of nutrition to the development of cognitive decline and Alzheimer’s disease.

Highlights

Alzheimer’s disease is one of the greatest global health challenges and the development of a successful cure has been hindered due to its complex aetiology
There was no change in the performance of the object memory task thought to be processed by the perirhinal cortex
Other studies using Novel object recognition (NOR) tasks to test the effect of a high–fat diet (HFD) on object memory in C57Bl/6J mice have found diverse effects[4]

Summary

Results

50% of the behavioural video data were blind scored by an independent observer. Blind scored data correlated highly with the original live scored data as follows (all n = 288): NOR (r = 0.82), OP (r = 0.80), OC (r = 0.74) and OPC (r = 0.79), all p < 0.001, confirming the validity of the results. High-fat diet causes rapid deficits in episodic memory. Following the switch to a HFD there was a rapid drop in the performance in the episodic memory task. High-fat diet causes concurrent deficits in spatial and contextual memory whilst object memory is maintained. In the episodic memory task the impairment in the HFDR group was reversed while HFD mice maintained the deficit (Fig. 2A). In the spatial and contextual memory tasks, the impairment in the HFDR group was reversed while HFD mice maintained the deficits (Fig. 2B,C). The HFDR and HFD groups maintained the ability to perform the object memory task throughout (Fig. 2D). Following the switch back to LFD, the HFDR mice showed a significant reduction in caloric intake compared to HFD mice and compared to LFD mice. Detailed statistical analysis of IPGTT data can be found in Supplementary Information

Discussion

Findings

Methods