Brenton, Jonathan;
(2023)
Novel Brain Networks Influenced by Ageing: Effects on Gene Expression and Synapses of Diet-Induced Obesity.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Obesity and ageing are contributing factors to many diseases and deaths across the world. Both are also linked to cognitive decline, synaptic dysfunction and brain volume loss outside of a disease context. Since these factors have shown similar outcomes, it has been hypothesised that an interaction between them may exacerbate mutual pathology. Investigation of the interaction of these two conditions may identify the pathways and mechanisms underlying obesity-related and age-related cognitive dysfunction in the brain. The current work studied a HFD mouse model of obesity across age, from adulthood to the end of mid-life, to discover the impact of the interaction ageing and obesity on synaptic transmission and gene expression. The metabolic and physiological outcomes of the HFD model across age were characterised as well as synaptic transmission and plasticity at 6 and 18 months. A reversal of the HFD to a chow LFD during mid-life to early old age (14-18 months) was used to examine if diet reversal could alter the negative outcomes caused by obesity. The current study found that high-fat diet caused extreme gain in weight, hyperphagia and hyperglycaemia that was maintained across the lifespan, as well as decreased survival and an increased liver cancer rate. No changes in excitatory glutamatergic transmission were found due to an interaction between ageing and obesity. Gene expression analysis found no clear effect of this interaction upon genetic pathways associated with ageing or obesity. However, postsynaptic changes due to the effect of obesity were identified at 18 months of age. A reversal of the HFD removed the HFD-induced weight gain and hyperglycaemia but had no impact upon synaptic transmission. Therefore the current work did not find that the interaction between age and obesity had strong effects upon synaptic transmission and genetic pathways from adulthood to the end of mid-life in the hippocampus.
Type: | Thesis (Doctoral) |
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Qualification: | Ph.D |
Title: | Novel Brain Networks Influenced by Ageing: Effects on Gene Expression and Synapses of Diet-Induced Obesity |
Open access status: | An open access version is available from UCL Discovery |
Language: | English |
Additional information: | Copyright © The Author 2022. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept |
URI: | https://discovery.ucl.ac.uk/id/eprint/10164478 |
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