Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.580127
Title: Identification of biomolecular pathways associated with the central nervous system based symptoms of Gulf War Illness
Author: Abdullah, Laila
ISNI:       0000 0004 2745 5275
Awarding Body: Open University
Current Institution: Open University
Date of Award: 2012
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Abstract:
The clinical profile of GWI is characterized by the presence the central nervous systems (CNS) symptoms which include memory impairment, anxiety, widespread pain and motor problems. Now, even twenty years later, veterans with GWI continue to suffer from these persistent symptoms. Currently, there is no treatment available for treating GWI, which is largely due to the complexity of the clinical presentation of this illness and the heterogeneity of GW exposures. The main goals of this thesis were to develop and characterize GW agent exposure mouse models that recapitulate the CNS symptoms of GWI and to identify the underlying aberrant biological pathways. Three major objectives were undertaken to accomplish these goals: (1) Two mouse models of GW-agent exposure were developed using combination of the anti-nerve gas treatment pyridostigmine bromide (PB), pesticides (permethrin), an insect repellent (N,N-Diethyl-meta-toluamide) and stress. Neurobehavioral studies show that combined exposure to GW agents produced anxiety and sensorimotor deficits in one mouse model and anxiety and cognitive impairment in the other. Neuropathological studies showed a presence of astrogliosis in both models. (2) Exploratory proteomic studies suggested that lipid-metabolism and immune/inflammation were associated with GW-agent exposure. (3) As lipid dysfunction is upstream of the inflammatory pathways, a lipidomics approach was used to identify the GW-agent exposure dependent lipid profiles. Lipid profiles of mouse models of GW-agent exposure were compared with those of other neurological conditions to identify profiles that were unique to GW-agent exposure. Lipid profiles were interrogated to identify lipid-metabolism pathways that may be amenable to therapeutic targeting. Studies described in this thesis provide novel insight into the pathobiology of GWI and suggest that pathways involved in phosphatidylcholine metabolism might be of therapeutic value in treating the CNS symptoms of GWI.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.580127  DOI:
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