Protease-activated receptors (PARs) are a novel group of G protein coupled receptors with PAR1 and PAR2 expressed within the brain. Evidence from current literature shows that PAR4 is involved in neuronal activities, such as in ischaemic neuron apoptosis, as well as the involvement of its signalling pathways in neuropathic pain and inflammation. Recently, a study has also shown that PAR4 activation increases the expression of the hormone calcitonin protein and peptide mRNA in neurons localised in the dorsal root ganglions. Despite this evidence, the role of PAR4 within the CNS remains unclear. In platelets, PAR4 can be activated by thrombin and the PAR4-activating peptide, AYPGKF. Therefore, we used this peptide to investigate the role of PAR4 in the CNS.With PAR1 and PAR2 involvement in the CNS, we hypothesise that PAR4 activation will modulate neuronal and astrocytic function. PAR4 expression in the neurons and astrocytes was investigated using both primary cultures from both C57Bl6J mice and Sprague Dawley rats, with each showing the expression of PAR4. Using neuronal marker microtubule-associated protein 2 (MAP2), and astrocytic marker Glial fibrillary acidic protein (GFAP), we found PAR4 present in neurons and astrocytes. With current literature providing the data to demonstrate PAR2 is neuroprotective, we used kainate (100μM), a potent neurotoxic agent and propidium iodide to investigate PAR4 activation on cell viability.Treating primary hippocampal cell cultures with AYPGKF (50μM) alone was not toxic to the cultures but co-application of AYPGKF and kainate resulted in significant decrease in cell death (N ≥ 50 cells from 3 separate cultures. *=p
| Date of Award | 16 May 2022 |
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| Original language | English |
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| Awarding Institution | - University Of Strathclyde
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| Supervisor | Trevor Bushell (Supervisor) |
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