The Role of Brain Microvascular Endothelial Cell and Blood-Brain Barrier Dysfunction in Schizophrenia

Sovannarath Pong, Rakesh Karmacharya, Marianna Sofman, Jeffrey R. Bishop, Paulo Lizano

Research output: Contribution to journalReview articlepeer-review

41 Scopus citations

Abstract

Background: Despite decades of research, little clarity exists regarding pathogenic mechanisms related to schizophrenia. Investigations on the disease biology of schizophrenia have primarily focused on neuronal alterations. However, there is substantial evidence pointing to a significant role for the brain's microvasculature in mediating neuroinflammation in schizophrenia. Summary: Brain microvascular endothelial cells (BMEC) are a central element of the microvasculature that forms the blood-brain barrier (BBB) and shields the brain against toxins and immune cells via paracellular, transcellular, transporter, and extracellular matrix proteins. While evidence for BBB dysfunction exists in brain disorders, including schizophrenia, it is not known if BMEC themselves are functionally compromised and lead to BBB dysfunction. Key Messages: Genome-wide association studies, postmortem investigations, and gene expression analyses have provided some insights into the role of the BBB in schizophrenia pathophysiology. However, there is a significant gap in our understanding of the role that BMEC play in BBB dysfunction. Recent advances differentiating human BMEC from induced pluripotent stem cells (iPSC) provide new avenues to examine the role of BMEC in BBB dysfunction in schizophrenia.

Original languageEnglish (US)
Pages (from-to)30-46
Number of pages17
JournalComplex Psychiatry
Volume6
Issue number1-2
DOIs
StatePublished - Oct 1 2020

Bibliographical note

Publisher Copyright:
© 2020 The Author(s) Published by S. Karger AG, Basel.

Keywords

  • Brain microvascular endothelial cells
  • Efflux/influx transporter
  • Extracellular matrix
  • Induced pluripotent stem cells
  • Paracellular junction
  • Schizophrenia

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