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Fatty acid and lipid profiles in models of neuroinflammation and mood disorders. Application of high field NMR, gas chromotography and liquid chromotography-tandem mass spectrometry to investigate the effects of atorvaststin in brain and liver lipids and explore brain lipid changes in the FSL model of depression.
Anyakoha, Ngozi G.
Anyakoha, Ngozi G.
Publication Date
2010-06-08T14:51:43Z
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The University of Bradford theses are licenced under a Creative Commons Licence.
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Accepted for publication
Institution
University of Bradford
Department
School of Pharmacy
Awarded
2009
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Abstract
Lipids are important for the structural and physiological functions of neuronal cell
membranes. Alterations in their lipid composition may result in membrane dysfunction
and subsequent neuronal deficits that characterise various disorders. This study
focused on profiling lipids of aged and LPS-treated rat brain and liver tissue with a view
to explore the effect of atorvastatin in neuroinflammation, and examining lipid changes
in different areas of rat brain of the Flinders Sensitive Line (FSL) rats, a genetic model
of depression.
Lipids and other analytes extracted from tissue samples were analysed with proton
nuclear magnetic resonance spectroscopy (1H-NMR), gas chromatography (GC) and
liquid chromatography-tandem mass spectroscopy (LC/ESI-MS/MS).
Changes in the lipid profiles suggested that brain and liver responded differently to
ageing and LPS-induced neuroinflammation. In the aged animals, n-3 PUFA were
reduced in the brain but were increased in the liver. However, following treatment with
LPS, these effects were not observed. Nevertheless, in both models, brain
concentration of monounsaturated fatty acids was increased while the liver was able to
maintain its monounsaturated fatty acid concentration. Atorvastatin reversed the
reduction in n-3 PUFA in the aged brain without reducing brain and liver concentration
of cholesterol. These findings further highlight alterations in lipid metabolism in agerelated
neuroinflammation and show that the anti-inflammatory actions of atorvastatin
may include a modulation of fatty acid metabolism.
When studying the FSL model, there were differences in the lipid profile of different
brain areas of FSL rats compared to Sprague-Dawley controls. In all brain areas,
arachidonic acid was increased in the FSL rats. Docosahexaenoic acid and ether lipids
were reduced, while cholesterol and sphingolipids were increased in the hypothalamus
of the FSL rats. Furthermore, total diacylglycerophospholipids were reduced in the
prefrontal cortex and hypothalamus of the FSL rats. These results show differences in
the lipid metabolism of the FSL rat brain and may be suggestive of changes occurring
in the brain tissue in depression.
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Type
Thesis
Qualification name
PhD