Proteomic and Metabolomic Characterization of Human Neurovascular Unit Cells in Response to Methamphetamine

Abstract

The functional state of the neurovascular unit (NVU), composed of the blood–brain barrier and the perivasculature that forms a dynamic interface between the blood and the central nervous system (CNS), plays a central role in the control of brain homeostasis and is strongly affected by CNS drugs. Human primary brain microvascular endothelium, astrocyte, pericyte, and neural cell cultures are often used to study NVU barrier functions as well as drug transport and efficacy; however, the proteomic and metabolomic responses of these different cell types are not well characterized. Culturing each cell type separately, using deep coverage proteomic analysis and characterization of the secreted metabolome, as well as measurements of mitochondrial activity, the responses of these cells under baseline conditions and when exposed to the NVU‐impairing stimulant methamphetamine (Meth) are analyzed. These studies define the previously unknown metabolic and proteomic profiles of human brain pericytes and lead to improved characterization of the phenotype of each of the NVU cell types as well as cell‐specific metabolic and proteomic responses to Meth.

Document Details

Document Type
Pub Defense Publication
Publication Date
Aug 03, 2020
Source ID
10.1002/adbi.201900230

Entities

People

  • Anna Herland
  • Ben M Maoz
  • Bogdan Budnik
  • Charles Vidoudez
  • Donald E. Ingber
  • Edward A FitzGerald
  • Kevin Kit Parker
  • Nikita Budnik
  • Robert Mannix
  • Sean P. Sheehy
  • Stephanie Dauth
  • Thomas Grevesse

Organizations

  • Defense Advanced Research Projects Agency
  • Harvard Medical School
  • Harvard University
  • Karolinska Institutet
  • Knut and Alice Wallenberg Foundation
  • Royal Institute of Technology
  • Tel Aviv University

Tags

Fields of Study

  • Biology

Readers

  • Molecular and genetic basis of cancer.
  • Neuroscience
  • Oncology (Cancer Research).

Technology Areas

  • Biotechnology