To Study Tauopathy Molecular Mechanism Upon Diabetes

Background: Diabetes mellitus (DM) is a metabolic disorder in which various organs are being affected. In particular, neural cells severely respond to the stress conditions caused by DM, resulting in neurodegeneration. There are two major pathologi-cal hallmarks playing part in the neurodegeneration including hyperphosphorylated tau (P-tau) and amyloid β plaques. Tau is a microtubule associated protein, which is moderately phospho-rylated under physiological conditions and is hyperphosphoryl-ated upon abnormal situations. It is well-documented that dia-betes can cause tau phosphorylation on different sites. Anyway, it s not clear that which tau phosphorylation site plays the criti-cal role in driving neurotoxicity and tauopathy upon Diabetes. Recently, It has been shown that phosphorylated tau at T231 exists in the two distinct cis and trans conformations in which that cis p-tau is extremely neurotoxic and can be accumulated in neurons cultured under nutrition depletion. These observations led us to hypothesis that DM can induce cis p-tau in type 1 and 2 diabetic mouse models.Materials and Methods: 70 mg/kg Alloxan was used to induce hyperglycemia in mice models. We performed immunostaining with cis p-tau monoclonal antibody after hyperglycemia induc-tion.Results: We observed cis p-tau at early stages of hyperglyce-mia in in vivo and in vitro models. Interestingly we have de-tected cis p-tau in specific brain regions like corpus callosum and brain stem. Moreover, GABAergic and Glutamatergic neu-rons were significantly positive for cis p-tau compare to other neurons.Conclusion: Our findings demonstrate that Neurodegeneration, resulted by Diabetes, is being driven through cis p-tau and thus, prospective therapies against cis p-tau could be applicable for Diabetes. The results open new windows toward understanding the molecular mechanism of neurodegeneration upon DM.