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dc.contributor.advisorLizano, Pauloen_US
dc.contributor.advisorVanuytsel, Kimen_US
dc.contributor.authorPong, Sovannarathen_US
dc.date.accessioned2020-06-09T15:45:20Z
dc.date.issued2020
dc.identifier.urihttps://hdl.handle.net/2144/41156
dc.description.abstractDisruption of the blood-brain barrier (BBB) is hypothesized to play an important role in the disease biology of schizophrenia (SZ). Brain microvascular endothelial cells (BMECs) have paracellular and transcellular proteins, transporters, as well as important extracellular matrix proteins, which collectively contribute to maintaining proper BBB function. While previous studies have provided some insights into the role of the BBB in SZ pathophysiology, there is a significant gap in our understanding of the cellular-molecular underpinnings of its major component, BMECs. Human induced pluripotent stem cells (hiPSCs) provide an exciting new avenue for exploring the role of BMECs in SZ. We hypothesize that BMECs have intrinsic deficits that lead to BBB dysfunction in SZ. In this study, we first aimed to test whether the existing hiPSC-derived BMEC protocols work with our patient-specific hiPSC samples. Secondly, we sought to investigate any potential deficits between BMECs derived from healthy control (HC) and SZ subjects. We successfully adapted the established protocol and confirmed the identity of these hiPSC-derived BMECs with relevant cell markers such as CLDN5, OCLN, TJP1, PECAM1, and SLC2A1. We also evaluate barrier function by measuring trans-endothelial electrical resistance (TEER) and efflux transporters activity of ABCB1 and ABCC1. We observed evidence of poor cellular adhesion and disrupted tight junctions in a subset of SZ hiPSC-derived BMECs, where approximately 70% of them demonstrated extensive BBB disruption (reduced TEER). These findings suggest that there may be cell-autonomous disease-specific deficits in BMECs in SZ that result in BBB dysfunction.en_US
dc.language.isoen_US
dc.subjectBiologyen_US
dc.subjectBlood-brain barrieren_US
dc.subjectBrain microvascular endothelial cellen_US
dc.subjectPsychosisen_US
dc.subjectSchizophreniaen_US
dc.titleBrain microvascular endothelial cell dysfunction in schizophrenia: a preliminary reporten_US
dc.typeThesis/Dissertationen_US
dc.date.updated2020-06-08T04:01:06Z
dc.description.embargo2022-06-07T00:00:00Z
etd.degree.nameMaster of Scienceen_US
etd.degree.levelmastersen_US
etd.degree.disciplineMedical Sciencesen_US
etd.degree.grantorBoston Universityen_US


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