OA诱导大鼠基底核Ach降低及τ蛋白过度磷酸化

研究了磷酸酯酶(proteinphosphatase，PP)对胆碱能神经元功能的影响，将PP抑制剂岗田酸(okadaic acid，OA)注入大鼠双侧Meynert基底核，并经免疫印迹检测r(tau)蛋白磷酸化程度、经微渗透结合HL,PC检测Ach、经Morris水迷宫检测大鼠的空间记忆能力，结果发现，Meynert基底核注射OA后，Ach水平降低，τ蛋白在Sei-198／Sei-199／Set-202，Ser-396／Ser-404位点发生过度磷酸化，并伴有大鼠空间记忆障碍，本研究结果提示PP活性降低可能参与了神经元纤维缠结形成、胆碱能神经元功能及认知功能障碍，在AD发病机制中起重要作用。

Hyperphosphorylation of tau and decrease of Ach level in the Meynert nucleus bas alis of rat brain induced by OA

To study the effect of protein phosphatase (PP) on functions of cholinergic neuron, a selective inhibitor of PP, okadaic acid (OA) was injected into the Meynert nucleus basalis of rats. The phosphorylation of tau by western-blot, the Ach level by microdialysis and HPLC, and the ability of special memory by Morris water maze were detected. It was found that injection of okadaic acid into the Meynert nucleus basalis of rat brain induced hyperphosphorylation of tau at Ser-198/Ser-199/Ser-202 and Ser-396/Ser-404 epitope, and decreased acetylcholine level accompanied with special memory deficit. The results indicated that down-regulation of PP participated in the loss of cholinergic neuron, formation of NTFs and clinical cognition deficit. It played an important role in the pathogenesis of AD.