Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Bucnik, B.
2-chlorohexadecanal and 2-chlorohexadecanoic acid as effectors of microglia polarization
Humanmedizin; [ Diplomarbeit ] Graz Medical University; 2016. pp.
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Bernhart Eva Maria
- Sattler Wolfgang
- Altmetrics:
- Abstract:
- Neuroinflammatory disorders and subsequent neurodegeneration are common in our modern society, thus representing an interesting target of research. The blood brain barrier, which provides protection and secures homeostasis within the central nervous system, plays an important role during neurological disorders like Alzheimer’s disease, Parkinson’s disease, multiple sclerosis or stroke. Studies showed that during oxidative stress the MPO-H2O2-halide system generates hypochlorous acid. This potent oxidant can attack ether-phospholipids, termed plasmalogens, which are important components of cell membranes and very common in the central nervous system. Their vinyl ether linkage is destroyed by hypochlorous acid, resulting in the formation of the a-chloro fatty aldehyde 2 chlorohexadecanal and the a-chloro fatty acid 2-chlorohexadecanoic acid. Under inflammatory conditions, microglia, the brain resident immune cells, are considered to occur in two different polarization states. The classically activated proinflammatory M1 phenotype is believed to be neurodestructive while the alternatively activated anti-inflammatory M2 microglia was shown to have neuroprotective potential. The aim of this thesis was to get preliminary insights into the effects of 2-chlorohexadecanal and 2-chlorohexadecanoic acid on BV 2 microglia polarization. For this purpose, cell viability was assessed with the MTT assay, which displayed the cytotoxic properties of 2-chlorohexadecanoic acid. 2-chlorohexadecanal treated cells were analyzed by western blot and flow cytometry after different timepoints post-treatment. The results of these experiments were controversial and remained inconclusive. No changes in the levels of reactive oxygen species and NO2-/NO3- were detected after 2-chlorohexadecanal treatment. Although definitive statements on classically and alternatively activated pathways cannot be made after these experiments, the important role of microglia is unquestionable. The understanding of the immunological response in CNS pathophysiology is key in order to discover better treatment options for patients with neuroinflammatory and neurodegenerative disorders.