Vascular and immune changes underlying the detrimental short-term effects of high-fat, high-calorie, diets

Clarke, Devin Kenneth (2020) Vascular and immune changes underlying the detrimental short-term effects of high-fat, high-calorie, diets. Doctoral thesis (PhD), University of Sussex.

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Abstract

Evidence suggests that diets high in fat and calories (HFD) can induce detrimental hippocampalspecific behavioural effects starting after as little as 24 hours on the diet. Such a rapid and regionspecific cognitive impact is unexpected given the brain is largely insulated from rapid peripheral changes by the blood-brain barrier (BBB). Understanding why this occurs will not only add valuable insight into how influential diets are on our brains, but could also help explain why the hippocampus appears to be one of the regions most sensitive to damage in a myriad of disease states, most prominently in Alzheimer’s Disease.

To investigate this I compared mice fed a HFD to those fed a control diet at numerous timepoints, and looked for changes in animal behaviour, microglial and immune responses in the brain, and changes in the brain’s blood supply. The techniques used to do this included behavioural tests, tissue immunostaining, antibody arrays, cranial window implantations, and confocal and two photon microscopy. I compared the measures between timepoints, diets, and brain regions - the hippocampus, cortex, and hypothalamus - to identify which of these measures appeared to change in a hippocampal-specific manner.

Results showed that HFD feeding disrupts the relationship between increased neural efficiency and cognitive performance in the hippocampus, with this perhaps driving early hippocampusspecific impairment. This disruption may be related to changes occurring in the vasculature, where HFD-induced capillary bed structural changes increase the resistance to blood flow. Shortterm HFD feeding also led to an increased density of microglial cells. This, and the capillary bed changes, were not region-specific, and my results suggest that these were likely translated to hippocampus-specific cognitive deficits due to the impoverished relationship between vascular support and neuronal metabolism in the hippocampus.

Item Type: Thesis (Doctoral)
Schools and Departments: School of Life Sciences > Neuroscience
Subjects: R Medicine > RA Public aspects of medicine > RA0421 Public health. Hygiene. Preventive Medicine > RA0784 Nutrition
R Medicine > RC Internal medicine > RC0321 Neurosciences. Biological psychiatry. Neuropsychiatry > RC0438 Psychiatry > RC0512 Psychopathology > RC0513 Psychoses > RC0521 Dementia > RC0522 Presenile dementia > RC0523 Alzheimer's disease
Depositing User: Library Cataloguing
Date Deposited: 10 Feb 2020 14:18
Last Modified: 10 Feb 2020 14:18
URI: http://sro.sussex.ac.uk/id/eprint/89655

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