过度磷酸化tau蛋白抑制海马DG区神经元的发生

Hyperphosphorylation Tau Inhibits Neurogenesis in the DG Region of Hippocampus

目的老年痴呆(Alzheimer's disease,AD)以tau蛋白过度磷酸化,淀粉样蛋白聚集为主要病理表现,同时出现神经发生紊乱。本研究探讨过度磷酸化的tau蛋白对神经发生的影响。方法通过在大鼠海马DG区定位注射冈田酸(OA)诱导过度磷酸化tau蛋白的AD模型,并通过5-溴脱氧尿嘧啶核苷(Brdu)标记,双皮质素(doublecortin,DCX)免疫组织化学染色,并通过计算切片上的标记细胞个数来判断神经元发生情况。使用水迷宫的方法检测模型鼠的学习记忆情况。结果 OA模型鼠表现出明显的学习和短期记忆障碍,PP2A特异性的tau蛋白过度磷酸化位点,包括丝氨酸404和262位点。虽然总的新生神经元没有明显差异,但是与对照组相比OA模型鼠中新生的神经元明显减少,说明过度磷酸化的tau蛋白抑制干细胞转化为神经元。结论过度磷酸化的tau蛋白可以抑制新生神经元的发生,同时也为AD的治疗提供了新的方向。

Objective Alzheimers disease （A D ） is characterized by hyperphosphorylation tau,amyloid aggregation. In AD the neurogenesisalso is disordered. We would explore the role of hyperphosphorylation tau in neurogenesis. Methods Okadaic acid （ OA） to make hyperphosphorylation tauas AD model. By injecting the OA into the dentate gyrus （DG） of hippocampus and staining by 5-bromo-2-deoxyuridine （Brdu） and Doublecortin （DCX） we want to explore the state of neurogenesis bythestatistics of labeledneurons. We also use the water maze to test the ability of rats＇ learning and memory. Results We found there were an obvious learning and short- memory damage and a PP2A specific tau hyperphosphorylation at the site of serine 404 and 262. In the region of DG no different was found in the new bom cell , but a huge decrease in the new neuron in AD model rats, which demonstrated hyperphosphorylation tau could inhibit the stem cell to differentiate to neurons. Conclusion Our research proved the hyperphosphorylation tau could inhibit neurogenesis and also provided new direction for therapy.