Cis pT231-tau Drives Neurodegeneration in Bipolar Disorder

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. Anyhow, 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 th...