An examination of the impact of dietary lipids on behaviour and neurochemistry

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dc.contributor.advisor Dinan, Ted G. en
dc.contributor.advisor Cryan, John F. en
dc.contributor.author Pusceddu, Matteo
dc.date.accessioned 2015-12-09T15:28:26Z
dc.date.available 2015-12-09T15:28:26Z
dc.date.issued 2015
dc.date.submitted 2015
dc.identifier.citation Pusceddu, M. 2015. An examination of the impact of dietary lipids on behaviour and neurochemistry. PhD Thesis, University College Cork. en
dc.identifier.endpage 215
dc.identifier.uri http://hdl.handle.net/10468/2132
dc.description.abstract The molecular and cellular basis of stress pathology remains an important research question in biological science. A better understanding of this may enable the development of novel approaches for the treatment of stress-related disorders. There is a considerable body of scientific evidence suggesting that dietary lipids, phospholipids and omega-3 polyunsaturated fatty acids (n-3 PUFAs), have therapeutic potential for certain psychiatric disorders. Thus, we proposed n-3 PUFAs as a novel strategy for the prevention or amelioration of stress-related disorders. We hypothesised that these compounds would improve behavioural and neurobiological responses and alter gut microbial composition. Furthermore, we proposed a new mechanism of action exerted by n-3 PUFAs using an in vitro model of stress. Lastly, we explored the protective effects of both phospholipids and n-3 PUFAs against neuroinflammation, which has been shown to contribute to the development of stress-related disorders. We provide further evidence that glucocorticoids, inflammation and early-life stress induce vulnerability to psychopathologies. Specifically, we have demonstrated that corticosterone (CORT) alters cortical neuron and astrocyte percentage composition, reduces brain-derived-neuronal factor (BDNF) expression, and induces glucocorticoid receptor (GR) down-regulation in mixed cortical cultures. Interestingly, we found that lipopolysaccharide (LPS) treatment resulted in an over-expression of pro-inflammatory cytokines in cortical astrocyte cultures. Moreover, we demonstrate that early-life stress induces changes to the monoaminergic and immune systems as well as altered neuroendocrine response to stressors later in life. In addition, we found that early-life stress alters the gut microbiota in adulthood. These data demonstrate that n-3 PUFAs can attenuate CORT-induced cellular changes, but not those caused by LPS, within the cerebral cortex. Similarly, phospholipids were unable to reverse LPS-induced inflammation in cultured astrocytes. In addition, this thesis proposes that n-3 PUFAs may prevent the development or lessen the symptoms of mental illnesses, ameliorating anxiety- and depressive-like symptoms as well as cognitive effects, particularly when administered during neurodevelopment. Such effects may be mediated by GR activation as well as by modification of the gut microbiota composition. Taken together, our findings suggest that n-3 PUFAs have therapeutic potential for stress-related disorders and we provide evidence for the mechanisms by which they may exert these effects. These findings contribute to an exciting and growing body of research suggesting that nutritional interventions may have an important role to play in the treatment of stress-related psychiatric conditions. en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher University College Cork en
dc.rights © 2015, Matteo Pusceddu. en
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/3.0/ en
dc.subject LPS en
dc.subject Stress en
dc.subject Animal behaviour en
dc.subject Corticosterone en
dc.subject Glucocorticoid receptor en
dc.subject Microbiota en
dc.subject Female rats en
dc.subject Primary culture en
dc.title An examination of the impact of dietary lipids on behaviour and neurochemistry en
dc.type Doctoral thesis en
dc.type.qualificationlevel Doctoral Degree (Structured) en
dc.internal.availability Full text available en
dc.check.info No embargo required en
dc.description.version Accepted Version
dc.description.status Not peer reviewed en
dc.internal.school Alimentary Pharmabotic Centre en
dc.internal.school Psychiatry en
dc.check.type No Embargo Required
dc.check.reason No embargo required en
dc.check.opt-out No en
dc.thesis.opt-out false
dc.check.embargoformat Not applicable en
ucc.workflow.supervisor t.dinan@ucc.ie
dc.internal.conferring Autumn Conferring 2015


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© 2015, Matteo Pusceddu. Except where otherwise noted, this item's license is described as © 2015, Matteo Pusceddu.
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