病理浓度甲醛的累积导致小鼠神经母瘤细胞活力及黏附能力下降

Formaldehyde (FA) plays a role in age-related cognitive impairment. An increase in endogenous FA induced by long-term oral administration of methanol, which triggers Tau hyperphosphorylation in the brain of Macaca mulatta and deteriorates the animal’s working memory. Short-term, high-dose FA treatment induces Tau hyperphosphorylation in the cytoplasm and nucleus of murine neural cells in vivo and in vitro. However, the pathological FA level is lower than that used in those experiments. The long-term effect on neural cells of FA at pathological doses has not yet been investigated. Here, based on the pathological level of endogenous FA in Alzheimer’s disease (AD) patients, we added 10 mmol/l (mM) FA to the medium and incubated murine neuroblastoma (N2a) cells for six days by using a serial passage strategy. FA-induced significant decreases in cell number and viability as well as increased lactate dehydrogenase (LDH) release were observed during the culture. Holographic microscopy showed that cells exposed to FA were thicker and smaller, exhibiting a weakened adhesive morphology. Immunofluorescence staining demonstrated that the pathological dose of FA increases Tau phosphorylation at Threonine (T181) and Serine (S396) epitopes over time. These results indicate that long-term exposure to a pathological concentration of FA causes the cell viability decline and even cell death under the experimental conditions

Accumulation of Simulated Pathological Level of Formaldehyde Decreases Cell Viability and Adhesive Morphology in Neuronal Cells