METHODS: Phospholipase C (PLC), phosphatidylinositol-3-kinase (PI3K), and mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathways activated by NT-3 were analyzed by means of field electrophysiological recordings in brain slices from control and 3-NP treated in the presence of specific inhibitors of the signaling pathways.
RESULTS: Using specific inhibitors, PLC, PI3K, and MEK/ERK signaling pathways contribute to NT3-mediated plasticity modulation in striatal tissue slices recorded from control animals. However, in the neurodegeneration model induced by 3-NP, the recovery of striatal LTD induced by NT-3 was prevented only by the PLC inhibitor. Moreover, the PLC signaling pathway appeared to trigger downstream activation of the endocannabinoid system, evidenced by AM 251, an inhibitor of the CB1 receptor, also hindered NT-3 plasticity recovery.
CONCLUSIONS: Our finding highlights the specific involvement of the PLC pathway in the neuroprotective effects of NT-3 in mitigating synaptic dysfunction under neurodegenerative conditions.
方法:磷脂酶C(PLC),磷脂酰肌醇-3-激酶(PI3K),和由NT-3激活的丝裂原激活的蛋白激酶(MEK)/细胞外信号调节激酶(ERK)途径通过在对照和3-NP存在的情况下处理的脑切片中的场电生理记录进行分析信号通路的特异性抑制剂。
结果:使用特异性抑制剂,PLC,PI3K,和MEK/ERK信号通路有助于在对照动物记录的纹状体组织切片中NT3介导的可塑性调节。然而,在3-NP诱导的神经变性模型中,仅通过PLC抑制剂阻止NT-3诱导的纹状体LTD的恢复。此外,PLC信号通路似乎触发内源性大麻素系统的下游激活,由AM251证明,CB1受体的抑制剂,也阻碍了NT-3塑性恢复。
结论:我们的发现强调了PLC通路在NT-3减轻神经退行性条件下突触功能障碍的神经保护作用中的具体参与。