| Autor: |
Naserkhaki R; Department of Brain and Cognitive Sciences, Cell Science Research Center , Royan Institute for Stem Cell Biology and Technology, ACECR , Tehran , Iran., Zamanzadeh S; Department of Molecular Biology , Islamic Azad University, Tehran Medical Sciences Branch , Tehran , Iran., Baharvand H; Department of Stem Cells and Developmental Biology, Cell Science Research Center , Royan Institute for Stem Cell Biology and Technology, ACECR , Tehran , Iran., Nabavi SM; Department of Brain and Cognitive Sciences, Cell Science Research Center , Royan Institute for Stem Cell Biology and Technology, ACECR , Tehran , Iran., Pakdaman H; Department of Neurology , Shahid Beheshti University of Medical Sciences , Tehran , Iran., Shahbazi S; Department of Brain and Cognitive Sciences, Cell Science Research Center , Royan Institute for Stem Cell Biology and Technology, ACECR , Tehran , Iran., Vosough M; Department of Regenerative Biomedicine, Cell Science Research Center , Royan Institute for Stem Cell Biology and Technology, ACECR , Tehran , Iran., Ghaedi G; Mostafa Khomeini Hospital, School of Medicine , Shahed University , Tehran , Iran., Barzegar A; Legal Medicine Research Center, Legal Medicine Organization , Tehran , Iran., Mirtorabi D; Legal Medicine Research Center, Legal Medicine Organization , Tehran , Iran., Hedayatshodeh M; Department of Emergency Medicine , Tehran University of Medical Sciences , Tehran , Iran., Ehsani E; Department of Biology, Roudehen Branch , Islamic Azad University , Roudehen , Iran., Falahati M; Department of Nanotechnology, Faculty of Advance Science and Technology, Pharmaceutical Sciences Branch , Islamic Azad University , Tehran , Iran., Hajipour MJ; Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute , Tehran University of Medical Sciences , Tehran , Iran., Shahpasand K; Department of Brain and Cognitive Sciences, Cell Science Research Center , Royan Institute for Stem Cell Biology and Technology, ACECR , Tehran , Iran. |
| Abstrakt: |
Bipolar disorder is a complex neuropsychiatric disorder, characterized by intermittent episodes of mania and depression. Recent studies have indicated argyrophilic grains, composed of hyperphosphorylated tau, are observable in postmortem brains of bipolar patients. It remains uncertain how tau hyperphosphorylation results in neurodegeneration upon the disease. Recent studies have demonstrated that phosphorylated tau at Thr231 exists in two distinct cis and trans conformations, in which cis pT231-tau is highly neurotoxic and acts as an early driver of tauopathy in several neurodegenerative diseases. We herein employed an in vitro model, which resembles some aspects of bipolar disorder, to study the cis p-tau mediatory role. We established GSK3β overexpressing SH-SY5Y cells and examined cell viability, cis p-tau formation, and lithium effects by immunofluorescence and flow cytometry. We found an increase in cis p-tau levels as well as viability decrease in the cell model. Furthermore, we discovered that lithium treatment inhibits cis p-tau formation, resulting in diminished cell death. We also examined BD and healthy human brain samples and detected cis p-tau in the patients' brains. Our results show that tauopathy, observed in bipolar disorder, is being mediated through cis p-tau and that a conformer could be the cause of neurodegeneration upon the disease. Our findings would suggest novel therapeutic target to fight the devastating disorder. |
