Obesity and type II diabetes are associated with dementia and Alzheimer's disease. A high-fat diet induces memory deficits in rodents, however, complex episodic-like memory, has not been tested. Episodic memory is the recollection of events using a “what-where-when/which” experience and is the first memory to be compromised in Alzheimer's disease. To identify a link between a high-fat diet and episodic memory, 12 week old, male, C57Bl/6 mice, were fed a semi purified high-fat or low-fat diet ad libitum and tested with object-place-context (episodic-like), novel object recognition, object-place (spatial) and object-context (contextual) memory tasks for up to 2 weeks. A separate group of animals were fed a high-fat diet for 1 week followed by a low-fat diet for 1 week. Animals were killed after 3 days, 1 week or 2 weeks on diet. Brains were kept frozen until the hippocampus was dissected and proteomics performed. Further studies were carried out in rat primary hippocampal cell cultures to investigate the impact of different fatty acids on neuronal dendritic morphology. We found that episodic-like memory is compromised after only one day of a high fat diet together with spatial and contextual tasks. The ability to carry out the novel object recognition test remained intact. Proteomic analysis of hippocampal tissue revealed changes in a number of proteins associated with metabolism, cell stress, cell signalling, inflammation and the cytoskeleton. High-fat diet induced changes were reversed by a low-fat diet. Hippocampal neuron cultures showed that long chain saturated fatty acid palmitic acid, a component of the high-fat diet used in the behavioural and proteomic studies, caused reduced dendritic arborisation whist n-3 polyunsaturated fat docosahexaenoic acid negated these effects. These data link high-fat diet to indices of hippocampal neuronal damage and memory deficits and have implications for the link between diet, obesity and cognitive decline.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:715439 |
| Date | January 2016 |
| Creators | McLean, Fiona Hamilton |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=231763 |
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