PMID- 31987007 OWN - NLM STAT- MEDLINE DCOM- 20210301 LR - 20210820 IS - 1559-7016 (Electronic) IS - 0271-678X (Print) IS - 0271-678X (Linking) VI - 40 IP - 7 DP - 2020 Jul TI - Endothelial-specific Crif1 deletion induces BBB maturation and disruption via the alteration of actin dynamics by impaired mitochondrial respiration. PG - 1546-1561 LID - 10.1177/0271678X19900030 [doi] AB - Cerebral endothelial cells (ECs) require junctional proteins to maintain blood-brain barrier (BBB) integrity, restricting toxic substances and controlling peripheral immune cells with a higher concentration of mitochondria than ECs of peripheral capillaries. The mechanism underlying BBB disruption by defective mitochondrial oxidative phosphorylation (OxPhos) is unclear in a mitochondria-related gene-targeted animal model. To assess the role of EC mitochondrial OxPhos function in the maintenance of the BBB, we developed an EC-specific CR6-interactin factor1 (Crif1) deletion mouse. We clearly observed defects in motor behavior, uncompacted myelin and leukocyte infiltration caused by BBB maturation and disruption in this mice. Furthermore, we investigated the alteration in the actin cytoskeleton, which interacts with junctional proteins to support BBB integrity. Loss of Crif1 led to reorganization of the actin cytoskeleton and a decrease in tight junction-associated protein expression through an ATP production defect in vitro and in vivo. Based on these results, we suggest that mitochondrial OxPhos is important for the maturation and maintenance of BBB integrity by supplying ATP to cerebral ECs. FAU - Lee, Min Joung AU - Lee MJ AD - Department of Medical Science, Chungnam National University, Daejeon, Republic of Korea. AD - Department of Biochemistry, Chungnam National University, Daejeon, Republic of Korea. AD - Infection Control Convergence Research Center, College of Medicine, Chungnam National University, Daejeon, Republic of Korea. FAU - Jang, Yunseon AU - Jang Y AD - Department of Medical Science, Chungnam National University, Daejeon, Republic of Korea. AD - Department of Biochemistry, Chungnam National University, Daejeon, Republic of Korea. AD - Infection Control Convergence Research Center, College of Medicine, Chungnam National University, Daejeon, Republic of Korea. FAU - Han, Jeongsu AU - Han J AUID- ORCID: 0000-0001-6524-9841 AD - Department of Medical Science, Chungnam National University, Daejeon, Republic of Korea. AD - Department of Biochemistry, Chungnam National University, Daejeon, Republic of Korea. FAU - Kim, Soo J AU - Kim SJ AD - Department of Medical Science, Chungnam National University, Daejeon, Republic of Korea. AD - Department of Biochemistry, Chungnam National University, Daejeon, Republic of Korea. AD - Infection Control Convergence Research Center, College of Medicine, Chungnam National University, Daejeon, Republic of Korea. FAU - Ju, Xianshu AU - Ju X AD - Department of Medical Science, Chungnam National University, Daejeon, Republic of Korea. AD - Infection Control Convergence Research Center, College of Medicine, Chungnam National University, Daejeon, Republic of Korea. FAU - Lee, Yu Lim AU - Lee YL AD - Department of Medical Science, Chungnam National University, Daejeon, Republic of Korea. AD - Infection Control Convergence Research Center, College of Medicine, Chungnam National University, Daejeon, Republic of Korea. FAU - Cui, Jianchen AU - Cui J AD - Department of Medical Science, Chungnam National University, Daejeon, Republic of Korea. AD - Infection Control Convergence Research Center, College of Medicine, Chungnam National University, Daejeon, Republic of Korea. FAU - Zhu, Jiebo AU - Zhu J AD - Department of Medical Science, Chungnam National University, Daejeon, Republic of Korea. AD - Department of Biochemistry, Chungnam National University, Daejeon, Republic of Korea. AD - Infection Control Convergence Research Center, College of Medicine, Chungnam National University, Daejeon, Republic of Korea. FAU - Ryu, Min Jeong AU - Ryu MJ AD - Department of Biochemistry, Chungnam National University, Daejeon, Republic of Korea. FAU - Choi, Song-Yi AU - Choi SY AD - Department of Pathology, Chungnam National University, Daejeon, Republic of Korea. FAU - Chung, Woosuk AU - Chung W AD - Department of Medical Science, Chungnam National University, Daejeon, Republic of Korea. AD - Department of Anesthesiology and Pain Medicine, School of Medicine, Chungnam National University, Daejeon, Republic of Korea. AD - Department of Anesthesiology and Pain medicine, Chungnam National University Hospital, Daejeon, Republic of Korea. FAU - Heo, Chaejeong AU - Heo C AD - Center for Integrated Nanostructure Physics (CINAP), Institute for Basic Science (IBS), Suwon, South Korea. AD - Center for Neuroscience Imaging Research (CNIR), Institute for Basic Science (IBS), Suwon, South Korea. FAU - Yi, Hyon-Seung AU - Yi HS AD - Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Republic of Korea. FAU - Kim, Hyun Jin AU - Kim HJ AD - Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Republic of Korea. FAU - Huh, Yang H AU - Huh YH AD - Electron Microscopy Research Center, Korea Basic Science Institute, Cheongju, Chungcheongbukdo, Republic of Korea. FAU - Chung, Sookja K AU - Chung SK AD - Medical Faculty at Macau University of Science and Technology, Taipa, Macau. FAU - Shong, Minho AU - Shong M AD - Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Republic of Korea. AD - Research Center for Endocrine and Metabolic Diseases, Chungnam National University School of Medicine, Daejeon, Republic of Korea. FAU - Kweon, Gi-Ryang AU - Kweon GR AD - Department of Medical Science, Chungnam National University, Daejeon, Republic of Korea. AD - Department of Biochemistry, Chungnam National University, Daejeon, Republic of Korea. FAU - Heo, Jun Young AU - Heo JY AUID- ORCID: 0000-0002-0859-0063 AD - Department of Medical Science, Chungnam National University, Daejeon, Republic of Korea. AD - Department of Biochemistry, Chungnam National University, Daejeon, Republic of Korea. AD - Infection Control Convergence Research Center, College of Medicine, Chungnam National University, Daejeon, Republic of Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200127 PL - United States TA - J Cereb Blood Flow Metab JT - Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism JID - 8112566 RN - 0 (Actins) RN - 0 (Cell Cycle Proteins) RN - 0 (Crif1 protein, mouse) SB - IM EIN - J Cereb Blood Flow Metab. 2020 Apr 11;:271678X20917043. PMID: 32281505 MH - Actins/*metabolism MH - Animals MH - Behavior, Animal MH - Blood-Brain Barrier/*metabolism/pathology MH - Capillary Permeability MH - Cell Culture Techniques MH - Cell Cycle Proteins/genetics/*metabolism MH - Endothelial Cells/*metabolism/pathology MH - Gene Knockdown Techniques MH - Mice MH - Mice, Knockout MH - Mice, Transgenic MH - Microvessels/*metabolism/ultrastructure MH - Mitochondria/*metabolism/pathology MH - Oxygen Consumption/physiology MH - Transfection PMC - PMC7308523 OTO - NOTNLM OT - ATP depletion OT - Crif1 OT - blood-brain barrier OT - endothelial cells OT - mitochondrial OxPhos EDAT- 2020/01/29 06:00 MHDA- 2021/03/02 06:00 PMCR- 2021/01/27 CRDT- 2020/01/29 06:00 PHST- 2020/01/29 06:00 [pubmed] PHST- 2021/03/02 06:00 [medline] PHST- 2020/01/29 06:00 [entrez] PHST- 2021/01/27 00:00 [pmc-release] AID - 10.1177_0271678X19900030 [pii] AID - 10.1177/0271678X19900030 [doi] PST - ppublish SO - J Cereb Blood Flow Metab. 2020 Jul;40(7):1546-1561. doi: 10.1177/0271678X19900030. Epub 2020 Jan 27.