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PTEN expression in astrocytic processes after spinal cord injury.
Molecular and Cellular Neuroscience ( IF 2.6 ) Pub Date : 2018-02-15 , DOI: 10.1016/j.mcn.2018.02.008
T V Povysheva 1 , Y O Mukhamedshina 2 , A A Rizvanov 3 , Y A Chelyshev 4
Affiliation  

The role of the Rho/ROCK/PTEN signaling pathway in the regulation of astrocyte function for consolidation/stabilization of the synapse has not been thoroughly studied. In this study, the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in GFAP-positive astrocytic processes in the ventral horns (VH) of the rat spinal cord has been evaluated in the normal condition and in a delayed period (30 days) after dosed contusion spinal cord injury (SCI) in caudal thoracic segments. In intact rats and at 30 days post-injury (dpi), semi-quantitative immunohistochemical analysis showed that there is approximately 2 folds less synaptophysin reactivity in the motoneuron perikarya than outside the perikarya, i.e., on dendritic spines, in the VH area. At 30 dpi, the square occupied by synaptophysin reactivity on the motoneuron perikarya and dendritic spines decreased ~2.4 and ~2.1 folds, respectively. Western blotting of the postsynaptic density protein 95 (PSD95) showed a decreased amount in the area of injury of ~3 folds at 30 dpi. Expression of GFAP in the astrocytic processes around the synaptophysin spots (APAS) was less than in the astrocytic processes that were located at distance from the synapses (APFS) both in the intact and SCI groups. In the APAS, the expression level of PTEN increased significantly after SCI. In these astrocytic processes, the PTEN expression level was significantly higher than in the APFS for both the intact and SCI rats. In the intact spinal cord, different PTEN expression levels were detected both in APAS and APFS. This may be due to the varying degree of integration of PTEN in the membrane compartment of astrocyte stem processes and possibly the increased delivery of PTEN from the GFAP-positive stem into fine GFAP-negative peripheral processes. The observed shifts after SCI reflect the imbalance in the mechanisms of synaptic plasticity after injury. Thus, strategies that have been developed for the deletion or knockdown of the PTEN gene are quite promising.

中文翻译:

脊髓损伤后星形胶质细胞过程中PTEN的表达。

Rho / ROCK / PTEN信号通路在星形胶质细胞功能的调节/突触巩固/稳定中的作用尚未得到充分研究。在这项研究中,已经评估了正常条件下和延迟时间内在大鼠脊髓腹角(VH)中GFAP阳性星形细胞过程中第10号染色体(PTEN)上缺失的磷酸酶和张力蛋白同源物的表达(30天数)在尾椎胸段挫伤性脊髓损伤(SCI)后进行。在完整的大鼠中,以及在损伤后第30天(dpi),半定量免疫组织化学分析显示,运动神经元骨核周围的突触素反应性比骨核周围(即在VH区的树突棘上)低约2倍。在30 dpi时,运动神经元周围核和树突棘被突触素反应性占据的平方分别降低了〜2.4倍和〜2.1倍。突触后密度蛋白95(PSD95)的Western印迹显示,在30 dpi时,损伤区域的数量减少了约3倍。在完整突触组和SCI组中,GFAP在突触素斑点周围(APAS)的星形胶质细胞过程中的表达均小于在距离突触(APFS)较远的星形胶质细胞过程中的表达。在APAS中,SCI后PTEN的表达水平显着增加。在这些星形细胞过程中,完整和SCI大鼠的PTEN表达水平均显着高于APFS。在完整的脊髓中,在APAS和APFS中均检测到不同的PTEN表达水平。这可能是由于PTEN在星形胶质干过程的膜区室中的整合程度不同,并且可能是由于PTEN从GFAP阳性茎到精细GFAP阴性外周过程的递送增加所致。SCI后观察到的变化反映了损伤后突触可塑性机制的不平衡。因此,已经开发出用于PTEN基因的缺失或敲除的策略是非常有前途的。
更新日期:2018-02-15
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