title: Proteomic analysis of the dorsal and ventral hippocampus of rats maintained on a high fat and refined sugar diet.
abstract: The typical Western diet, rich in high saturated fat and refined sugar (HFS), has been shown to increase cognitive decline with aging and Alzheimer's disease, and to affect cognitive functions that are dependent on the hippocampus, including memory processes and reversal learning. To investigate neurophysiological changes underlying these impairments, we employed a proteomic approach to identify differentially expressed proteins in the rat dorsal and ventral hippocampus following maintenance on an HFS diet. Rats maintained on the HFS diet for 8 weeks were impaired on a novel object recognition task that assesses memory and on a Morris Water Maze task assessing reversal learning. Quantitative label-free shotgun proteomic analysis was conducted on biological triplicates for each group. For the dorsal hippocampus, 59 proteins were upregulated and 36 downregulated in the HFS group compared to controls. Pathway ana-lysis revealed changes to proteins involved in molecular transport and cellular and molecular signaling, and changes to signaling pathways including calcium signaling, citrate cycle, and oxidative phosphorylation. For the ventral hippocampus, 25 proteins were upregulated and 27 downregulated in HFS fed rats. Differentially expressed proteins were involved in cell-to-cell signaling and interaction, and cellular and molecular function. Changes to signaling pathways included protein ubiquitination, ubiquinone biosynthesis, oxidative phosphorylation, and mitochondrial dysfunction. This is the first shotgun proteomics study to examine protein changes in the hippocampus following long-term consumption of a HFS diet, identifying changes to a large number of proteins including those involved in synaptic plasticity and energy metabolism. All MS data have been deposited in the ProteomeXchange with identifier PXD000028.
authors: Department of Psychology, Macquarie University, Sydney, NSW, Australia.
authors: Heather M
authors: HM
authors: Francis
authors: Mehdi
authors: M
authors: Mirzaei
authors: Margery C
authors: MC
authors: Pardey
authors: Paul A
authors: PA
authors: Haynes
authors: Jennifer L
authors: JL
authors: Cornish
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects; D059305:Diet, High-Fat; D004040:Dietary Carbohydrates / Q000494:pharmacology*; D002149:Energy Intake / Q000187:drug effects; D004924:Escape Reaction / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects; D005108:Extinction, Psychological / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D059748:Proteolysis / Q000187:drug effects; D020543:Proteome / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D054875:Ubiquitination / Q000187:drug effects
chemical_list: D004040:Dietary Carbohydrates; D020543:Proteome
keywords: Animal proteomics; Diet; Fat; Label-free quantitative proteomics; Nanoflow LC-MS/MS; Sugar