The rise in global obesity and related diseases, such as age-related cognitive decline and Alzheimer's disease, underlines the importance of understanding how nutrition can negatively impact human health, particularly cognition. Thus, the aim of this study was to identify changes in the hippocampus in a well-defined model of diet-induced obesity, the C57Bl/6 mouse on a high-fat diet (HFD). This follows on from our earlier study where hippocampal-dependent episodic memory was shown to be rapidly compromised by a HFD. To this end we fed mice a HFD for either 3 days, 1 week, 2 weeks, or 1 week HFD followed by 1 week low-fat diet (LFD). Proteomic analysis of mouse hippocampi identified altered expression patterns of proteins involved in metabolism, inflammation, cell stress, cell signalling, and the cytoskeleton which changed after only 3 days on a HFD and recovered rapidly on the LFD. The largest number of proteins changed were associated with the cytoskeleton including microtubule associated protein 2 (MAP2). Further experiments were carried out in hippocampal primary cell cultures immuno-stained for MAP2. Incubation of neurons with physiological levels of palmitic acid (PA), the most common long-chain saturated fatty acid in the diet, caused reduced dendritic length and arborisation. However the n-3 polyunsaturated fat, docosahexaenoic acid (DHA), had no effect and DHA in combination with PA negated the effects caused by PA. Hippocampal neurons treated with PA recovered rapidly when PA was removed. Dendrites are essential for cell communication, with dendritic spines forming the majority of post-synaptic sites, and are essential for neuronal plasticity. This study links diets high in saturated fats to indices of hippocampal neuronal damage and has implications for the link between diet, obesity and cognitive decline.
|Publication status||Published - Nov 2018|
|Event||onference: Society for Neuroscience 2018: 129. Brain Wellness and Aging: Metabolism, Oxidative Stress, and Cellular Mechanisms - San Diego, California, US, San Diego, UNITED STATES|
Duration: 4 Nov 2018 → 4 Apr 2019
|Conference||onference: Society for Neuroscience 2018|
|Period||4/11/18 → 4/04/19|