Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
Neuroscience. 2013 May 15;238:242-51. doi: 10.1016/j.neuroscience.2013.02.046. Epub 2013 Mar 1.
Alterations in axon-dendrite polarity impair functional recovery in the developing CNS after hypoxia-ischemia (HI) injury. PTEN (phosphatase and tensin homolog deleted on chromosome 10) signaling pathway mediates the formation of neuronal polarity. However, its role in cerebral HI injury is not fully understood. In this study, we investigated the role of PTEN pathway in regulation of axon-dendrite polarity using an oxygen-glucose deprivation (OGD) model with rat cortical neurons. We found that the activity of PTEN and glycogen synthase kinase 3β (GSK-3β) was increased after OGD, along with the decrease of the activity in protein kinase B (Akt) and collapsin response mediator protein-2 (CRMP-2). Pretreatment with bpv, a potent inhibitor of PTEN, caused a decrease of the activity in PTEN and GSK-3β, and a significant increase of the activity in Akt and CRMP-2. Simultaneously, the morphological polarity of neurons was maintained and neuronal apoptosis was reduced. Moreover, inhibition of PTEN rescued vesicle recycling in axons. These findings suggested that the PTEN/Akt/GSK-3β/CRMP-2 pathway is involved in the regulation of axon-dendrite polarity, providing a novel route for protecting neurons following neonatal HI.
轴突-树突极性的改变会损害缺氧缺血（HI）损伤后发育中中枢神经系统的功能恢复。PTEN（第 10 号染色体缺失的磷酸酶和张力蛋白同源物）信号通路介导神经元极性的形成。然而，其在大脑 HI 损伤中的作用尚未完全阐明。在这项研究中，我们使用大鼠皮质神经元的氧葡萄糖剥夺（OGD）模型研究了 PTEN 通路在调节轴突-树突极性中的作用。我们发现，OGD 后 PTEN 和糖原合酶激酶 3β（GSK-3β）的活性增加，同时蛋白激酶 B（Akt）和 collapsin 反应介质蛋白-2（CRMP-2）的活性降低。PTEN 的强效抑制剂 bpv 的预处理导致 PTEN 和 GSK-3β 的活性降低，Akt 和 CRMP-2 的活性显著增加。同时，神经元的形态极性得到维持，神经元凋亡减少。此外，抑制 PTEN 可挽救轴突中的囊泡回收。这些发现表明，PTEN/Akt/GSK-3β/CRMP-2 通路参与了轴突-树突极性的调节，为新生儿 HI 后保护神经元提供了新途径。
