Department of Histology, Cytology and Embryology, Kazan State Medical University, Kazan, Tatarstan, Russia.
Department of Histology, Cytology and Embryology, Kazan State Medical University, Kazan, Tatarstan, Russia; OpenLab Gene and Cell Technologies, Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, Kazan, Tatarstan, Russia.
Mol Cell Neurosci. 2018 Apr;88:231-239. doi: 10.1016/j.mcn.2018.02.008. Epub 2018 Feb 15.
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.
Rho/ROCK/PTEN 信号通路在调节星形胶质细胞功能以巩固/稳定突触中的作用尚未得到深入研究。在这项研究中，评估了磷酸酶和张力蛋白同源物缺失的第 10 号染色体（PTEN）在大鼠脊髓腹角（VH）GFAP 阳性星形胶质细胞突起中的表达，在正常情况下和剂量挫伤性脊髓损伤（SCI）后延迟期（30 天）。在完整的大鼠和损伤后 30 天（dpi），半定量免疫组织化学分析显示，运动神经元胞体中的突触小泡反应性约为胞体外部的 2 倍，即 VH 区域的树突棘。在 30 dpi 时，突触小泡反应性在运动神经元胞体和树突棘上占据的正方形分别减少了2.4 和2.1 倍。突触后密度蛋白 95（PSD95）的 Western blot 显示，在 30 dpi 时损伤区域的量减少了约 3 倍。在完整和 SCI 组中，GFAP 在突触小泡周围的星形胶质细胞突起（APAS）中的表达量均低于距突触有一定距离的星形胶质细胞突起（APFS）。在 APAS 中，SCI 后 PTEN 的表达水平显著增加。在这些星形胶质细胞突起中，PTEN 的表达水平在完整和 SCI 大鼠中均明显高于 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 在星形胶质细胞干突起的膜区室中的整合程度不同，并且可能是从 GFAP 阳性干突进入细的 GFAP 阴性周围突起的 PTEN 增加。SCI 后的观察到的变化反映了损伤后突触可塑性机制的失衡。因此，已经为 PTEN 基因的缺失或敲低开发的策略非常有前景。
