Lipid signaling is an essential biological event/process in a plethora of pathophysiological conditions. The underlying idea of this thesis is that many of the roles and the complex interplay of... Show moreLipid signaling is an essential biological event/process in a plethora of pathophysiological conditions. The underlying idea of this thesis is that many of the roles and the complex interplay of the individual signaling lipids in inflammatory processes and related conditions in health and disease is not well known, and therefore has to be studied integrally as a complex network. In order to study this complex interplay, an improved broad analytical method is necessary to analyze a wide range of different signaling lipid classes such as oxylipins, (nitro) free fatty acids, endocannabinoids, bile acids and different subclasses of lysophospholipids. Therefore, the aim of this thesis is to develop a better method to study signaling lipids, and to apply it to study the role of these molecules in several relevant biological questions for a better understanding of inflammation related pathophysiology including autoimmune diseases, neurodegeneration and regulatory effect of exercise training. Show less
The main objective of this thesis was to investigate the serotonergic and cholinergic neurotransmitter systems, and the way these are altered in older age and Alzheimer’s disease. For that purpose,... Show moreThe main objective of this thesis was to investigate the serotonergic and cholinergic neurotransmitter systems, and the way these are altered in older age and Alzheimer’s disease. For that purpose, the neuroimaging technique resting state fMRI (RS-fMRI) was used to measure whole brain functional connectivity with and without pharmacological stimulation. The first part of the thesis concerns two pharmacological RS-fMRI studies that were executed in young adults. Pharmacological challenge effects of two selective serotonin reuptake inhibitors (sertraline and citalopram) and a cholinesterase inhibitor (galantamine) on brain connectivity were examined to gain more insight into the underlying neurotransmitter systems and the mechanisms of drug action in the central nervous system. The second part of this thesis was aimed at discovering changes in brain connectivity and serotonergic and cholinergic system functioning in aging and Alzheimer’s disease, by comparing brain network connections and the pharmacological response of this measure between young and older adults and patients with Alzheimer’s disease. Show less
Early dementias are difficult to distinguish from normal age-related memory decline. In the preclinical stages of Alzheimer’s disease and Huntington’s disease, brain functions are already changing... Show moreEarly dementias are difficult to distinguish from normal age-related memory decline. In the preclinical stages of Alzheimer’s disease and Huntington’s disease, brain functions are already changing, but this is not directly visible from the outside. Many research is aimed at discovering early disease markers. However, research using EEG registration during conventional eyes closed conditions revealed little additional information. The yield of EEG research can be improved by probing the weakest spot, which, in case of dementia, is memory. Karin van der Hiele introduced memory tests during EEG registration and found that early abnormalities in brain functioning can then be observed in Alzheimer’s disease and Huntington’s disease. An interesting finding came to light: the EEG in dementia displays a lot of muscle activity which is normally filtered out. However, the researchers decided not to throw this activity away but to measure it. Interestingly, they found that the amount of muscle activity was related to cognition and to the number of depressive complaints. It may pay to keep an open mind regarding the nature of the parameter to be measured. Show less
