PMID- 32744807 OWN - NLM STAT- MEDLINE DCOM- 20211018 LR - 20211018 IS - 2366-7478 (Print) IS - 2366-7478 (Linking) VI - 4 IP - 9 DP - 2020 Sep TI - Proteomic and Metabolomic Characterization of Human Neurovascular Unit Cells in Response to Methamphetamine. PG - e1900230 LID - 10.1002/adbi.201900230 [doi] AB - 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. CI - (c) 2020 The Authors. Published by Wiley-VCH GmbH. FAU - Herland, Anna AU - Herland A AD - Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, 02115, USA. AD - Division of Micro and Nanosystems, KTH Royal Institute of Technology, Stockholm, 10044, Sweden. AD - AIMES, Center for the Advancement of Integrated Engineering and Medical Sciences, Department of Neuroscience, Karolinska Institute, Stockholm, 17177, Sweden. FAU - Maoz, Ben M AU - Maoz BM AD - Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, 02115, USA. AD - Disease Biophysics Group, Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA. AD - Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv, 6997801, Israel. AD - Department of Biomedical Engineering, Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, 6997801, Israel. FAU - FitzGerald, Edward A AU - FitzGerald EA AD - Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, 02115, USA. FAU - Grevesse, Thomas AU - Grevesse T AD - Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, 02115, USA. AD - Disease Biophysics Group, Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA. FAU - Vidoudez, Charles AU - Vidoudez C AD - Small Molecule Mass Spectrometry Facility, Harvard University, Cambridge, MA, 02138, USA. FAU - Sheehy, Sean P AU - Sheehy SP AD - Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, 02115, USA. AD - Disease Biophysics Group, Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA. FAU - Budnik, Nikita AU - Budnik N AD - Disease Biophysics Group, Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA. FAU - Dauth, Stephanie AU - Dauth S AD - Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, 02115, USA. AD - Disease Biophysics Group, Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA. FAU - Mannix, Robert AU - Mannix R AD - Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, 02115, USA. FAU - Budnik, Bogdan AU - Budnik B AD - Mass Spectrometry and Proteomics Resource Laboratory, Harvard University, Cambridge, MA, 02138, USA. FAU - Parker, Kevin Kit AU - Parker KK AD - Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, 02115, USA. AD - Disease Biophysics Group, Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA. FAU - Ingber, Donald E AU - Ingber DE AUID- ORCID: 0000-0002-4319-6520 AD - Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, 02115, USA. AD - Vascular Biology Program and Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA. AD - Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20200803 PL - Germany TA - Adv Biosyst JT - Advanced biosystems JID - 101711718 RN - 0 (Central Nervous System Stimulants) RN - 0 (Proteome) RN - 44RAL3456C (Methamphetamine) SB - IM MH - Astrocytes/cytology/drug effects MH - Brain/blood supply/cytology MH - Cells, Cultured MH - Central Nervous System Stimulants/pharmacology MH - Endothelial Cells/cytology/drug effects MH - Humans MH - Metabolome/*drug effects MH - Metabolomics MH - Methamphetamine/*pharmacology MH - *Neurons/cytology/drug effects MH - *Pericytes/cytology/drug effects MH - Proteome/analysis/*drug effects MH - Proteomics OTO - NOTNLM OT - brain in vitro models OT - methamphetamine OT - neurovascular unit OT - primary cells EDAT- 2020/08/04 06:00 MHDA- 2021/10/21 06:00 CRDT- 2020/08/04 06:00 PHST- 2019/09/20 00:00 [received] PHST- 2020/07/02 00:00 [revised] PHST- 2020/08/04 06:00 [pubmed] PHST- 2021/10/21 06:00 [medline] PHST- 2020/08/04 06:00 [entrez] AID - 10.1002/adbi.201900230 [doi] PST - ppublish SO - Adv Biosyst. 2020 Sep;4(9):e1900230. doi: 10.1002/adbi.201900230. Epub 2020 Aug 3.