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Title: The role of the proteoglycans OMD and PRELP in the maintenance of brain vasculature
Author: Davaapil, H.
ISNI:       0000 0004 7232 4493
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2018
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OMD and PRELP are proteoglycans belonging to the family of small leucine-rich repeat proteoglycans (SLRPs), whose members have been shown to modulate a variety of cellular processes, including migration, proliferation and differentiation. Abrogated expression of SLRP members has been linked to a multitude of developmental, age-related and inflammatory diseases. Previous work from the Ohnuma lab has shown that OMD and PRELP are strongly expressed in brain vasculature, and in this study, I aim to extend the understanding of OMD and PRELP in the context of vascular homeostasis. The cellular localisation of OMD and PRELP was investigated and I determined that OMD is weakly expressed in neurons, whereas PRELP is expressed in pericytes, vascular smooth muscle cells, microglia and ependymal cells. I have shown that there is vascular dysfunction in PRELP-/- mice. There is increased blood vessel content in the brain, accompanied by blood brain barrier (BBB) breakdown. Analysis of BBB components indicates basement membrane components laminin and perlecan are down-regulated in addition to coverage by pericytes and astrocyte end-feet. PRELP-/- mice also exhibit weakened adherens- and tight-junctions between endothelial cells. I have determined that OMD-/- brain vasculature is comparable to that of wild-type. I propose that PRELP has a role in maintaining vascular function. PRELP may modulate the stability of the BBB by acting as a bridging molecule for basement membrane proteins.
Supervisor: Ohnuma, S-I. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available