Formaldehyde induces hyperphosphorylation and polymerization of Tau protein both in vitro and in vivo

Background Chronic formaldehyde exposure leads to memory impairment and abnormal elevation of endogenous formaldehyde has been found in the brains of Alzheimer's disease (AD) patients. Hyperphosphorylated Tau protein with subsequent aggregates as neurofibrillary tangles (NFTs) is one of the typical pathological characteristics in AD brains. The mechanism underlying abnormally elevated concentrations of endogenous formaldehyde that induce Tau hyperphosphorylation is unknown. Methods N2a cells and mice were treated with formaldehyde for different time points, then Western blotting and immunocytochemistry were utilized to determine the phosphorylation and polymerization of Tau protein. HPLC was used to detect the concentration of formaldehyde in cell media. Results Under formaldehyde stress, Tau became hyperphosphorylated, not only in the cytoplasm, but also in the nucleus of neuroblastoma (N2a) cells, and mouse brains. Polymers of cellular phospho-Tau were also detected. Significant accumulation of glycogen synthase kinase-3β (GSK-3β) in the nucleus of N2a and mouse brain cells, and elevation of its phosphorylation at Y216, was observed under formaldehyde stress. Formaldehyde-induced Tau hyperphosphorylation was blocked in the presence of LiCl and CT99021, inhibitors of GSK-3β, and by RNAi interference. Conclusions Formaldehyde, which may cause age-related memory loss, can act as a factor triggering Tau hyperphosphorylation via GSK-3β catalysis and induces polymerization of Tau. General significance Investigation of formaldehyde-induced Tau hyperphosphorylation may provide novel insights into mechanisms underlying tauopathies

A-Site and B-Site Charge Orderings in an s–d Level Controlled Perovskite Oxide PbCoO 3_{3}

Perovskite PbCoO3 synthesized at 12 GPa was found to have an unusual charge distribution of Pb2+Pb4+3Co2+2Co3+2O12 with charge orderings in both the A and B sites of perovskite ABO3. Comprehensive studies using density functional theory (DFT) calculation, electron diffraction (ED), synchrotron X-ray diffraction (SXRD), neutron powder diffraction (NPD), hard X-ray photoemission spectroscopy (HAXPES), soft X-ray absorption spectroscopy (XAS), and measurements of specific heat as well as magnetic and electrical properties provide evidence of lead ion and cobalt ion charge ordering leading to Pb2+Pb4+3Co2+2Co3+2O12 quadruple perovskite structure. It is shown that the average valence distribution of Pb3.5+Co2.5+O3 between Pb3+Cr3+O3 and Pb4+Ni2+O3 can be stabilized by tuning the energy levels of Pb 6s and transition metal 3d orbitals

A‑Site and B‑Site Charge Orderings in an <i>s–d</i> Level Controlled Perovskite Oxide PbCoO₃

Perovskite PbCoO₃ synthesized at 12 GPa was found to have an unusual charge distribution of Pb²⁺Pb⁴⁺₃Co²⁺₂Co³⁺₂O₁₂ with charge orderings in both the A and B sites of perovskite ABO₃. Comprehensive studies using density functional theory (DFT) calculation, electron diffraction (ED), synchrotron X-ray diffraction (SXRD), neutron powder diffraction (NPD), hard X-ray photoemission spectroscopy (HAXPES), soft X-ray absorption spectroscopy (XAS), and measurements of specific heat as well as magnetic and electrical properties provide evidence of lead ion and cobalt ion charge ordering leading to Pb²⁺Pb⁴⁺₃Co²⁺₂Co³⁺₂O₁₂ quadruple perovskite structure. It is shown that the average valence distribution of Pb^3.5+Co^2.5+O₃ between Pb³⁺Cr³⁺O₃ and Pb⁴⁺Ni²⁺O₃ can be stabilized by tuning the energy levels of Pb 6<i>s</i> and transition metal 3<i>d</i> orbitals