PMID- 31078687 OWN - NLM STAT- MEDLINE DCOM- 20200131 LR - 20200131 IS - 1873-7544 (Electronic) IS - 0306-4522 (Linking) VI - 410 DP - 2019 Jul 1 TI - gamma-Synuclein Induces Human Cortical Astrocyte Proliferation and Subsequent BDNF Expression and Release. PG - 41-54 LID - S0306-4522(19)30315-X [pii] LID - 10.1016/j.neuroscience.2019.04.057 [doi] AB - gamma-Synuclein (gamma-syn) is expressed by astrocytes in the human nervous system, and increased extracellularly in the brain and cerebrospinal fluid of individuals diagnosed with Alzheimer's disease. Upregulation of gamma-syn also coincides with proliferation of glioblastomas and other cancers. In order to better understand regulation and function of extracellular gamma-syn, primary human cortical astrocytes were treated with gamma-syn conditioned media at various physiological concentrations (50, 100, 150 nM) after cell synchronization. Additionally, extracellular brain-derived neurotrophic factor (BDNF), a neuroprotective growth factor released by astrocytes that has been shown to be decreased extracellularly in neurodegenerative disease, was observed in response to gamma-syn treatment. Analysis of 5-bromodeoxyuridine (BrdU) and propidium iodide through flow cytometry 24 h after release from synchronization revealed an increase in G(2)/M phase of the cell cycle with 100 nM gamma-syn during initial cell division, an effect that was reversed at 48 h. However, increased extracellular BDNF was observed at 48 h with 100 nM and 150 nM gamma-syn treatment with no difference between controls at 24 h. Further analysis of cell cycle markers with immunocytochemistry of BrdU and Ki67 after treatment with 100 nM gamma-syn confirmed increased initial cell proliferation and decreased non-proliferating cells. Western blot analysis demonstrated increased gamma-syn levels after 100 nM treatment at 24 and 48 h, and increased pro-BDNF, mature BDNF and cell viability at 48 h. The results demonstrate that gamma-syn internalization by human cortical astrocytes causes upregulation of the cell cycle, followed by subsequent BDNF expression and release. CI - Copyright (c) 2019 IBRO. Published by Elsevier Ltd. All rights reserved. FAU - Winham, Cynthia L AU - Winham CL AD - Biology Department, Neuroscience Program, University of Hartford, West Hartford, CT 06117, United States of America. FAU - Le, Timmy AU - Le T AD - Biology Department, Neuroscience Program, University of Hartford, West Hartford, CT 06117, United States of America. FAU - Jellison, Evan R AU - Jellison ER AD - Department of Immunology, UCONN Health, Farmington, CT 06030, United States of America. FAU - Silver, Adam C AU - Silver AC AD - Biology Department, Neuroscience Program, University of Hartford, West Hartford, CT 06117, United States of America. FAU - Levesque, Aime A AU - Levesque AA AD - Biology Department, Neuroscience Program, University of Hartford, West Hartford, CT 06117, United States of America. FAU - Koob, Andrew O AU - Koob AO AD - Biology Department, Neuroscience Program, University of Hartford, West Hartford, CT 06117, United States of America. Electronic address: koob@hartford.edu. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190510 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (gamma-Synuclein) RN - 7171WSG8A2 (BDNF protein, human) SB - IM MH - Astrocytes/drug effects/*metabolism MH - Brain-Derived Neurotrophic Factor/*biosynthesis/genetics MH - Cell Proliferation/drug effects/*physiology MH - Cell Survival/drug effects/physiology MH - Cells, Cultured MH - Cerebral Cortex/cytology/drug effects/*metabolism MH - Gene Expression MH - Humans MH - gamma-Synuclein/*pharmacology OTO - NOTNLM OT - Alzheimer's OT - Synuclein OT - astrocyte OT - brain derived neurotrophic factor OT - glioblastoma OT - neurodegeneration EDAT- 2019/05/13 06:00 MHDA- 2020/02/01 06:00 CRDT- 2019/05/13 06:00 PHST- 2019/03/02 00:00 [received] PHST- 2019/04/29 00:00 [revised] PHST- 2019/04/30 00:00 [accepted] PHST- 2019/05/13 06:00 [pubmed] PHST- 2020/02/01 06:00 [medline] PHST- 2019/05/13 06:00 [entrez] AID - S0306-4522(19)30315-X [pii] AID - 10.1016/j.neuroscience.2019.04.057 [doi] PST - ppublish SO - Neuroscience. 2019 Jul 1;410:41-54. doi: 10.1016/j.neuroscience.2019.04.057. Epub 2019 May 10.