Askvig Jason M, Dalzell Talia S, Toumeh Nadia, Kuball Phillip T, Whiteman Sara T, Bye Erik W, Andersen Marissa J, McCarthy Michael G, Irmen Riley E, Bexell Sydney H, Benolken Molly M, Maruska Brooke L, Nordmann Shelby E
Department of Biology, Concordia College, Moorhead, MN, 56562, USA.
Heliyon. 2020 Mar 9;6(3):e03501. doi: 10.1016/j.heliyon.2020.e03501. eCollection 2020 Mar.
Mature mammalian CNS neurons often do not recover successfully following injury. To this point, unilateral lesion of the hypothalamo-neurohypophysial tract results in collateral sprouting from uninjured axons of the supraoptic nucleus (SON) in 35-day-old but not in 125-day-old rats. Thus, it appears that there are age-related changes within the SON that preclude the older rat from recovering following axotomy. We hypothesize that the intrinsic capacity for axon reorganization may depend, in part, on age-related alterations in cell adhesion molecules that allow normal astrocyte-neuron interactions in the SON. In support of our hypothesis, numerous reports have shown that Thy-1 is increased in neurons at the cessation of axon outgrowth. Therefore, we compared protein levels of Thy-1 and the Thy-1 interacting integrin subunits, alpha-v (α), beta-3 (ß), and beta-5 (ß), in 35- and 125-day-old SON using western blot analysis. Our results demonstrated that there was significantly more Thy-1 protein in the 125-day-old SON compared to 35-day-old SON, but no change in the protein levels of the integrin subunits. Furthermore, we localized Thy-1-, α integrin-, ß integrin-, and ß integrin-immunoreactivity to both neurons and astrocytes in the SON. Altogether, our results suggest that the observed increase in Thy-1 protein levels in the SON with age may contribute to an environment that prevents collateral axonal sprouting in the SON of the 125-day-old rat.
成熟的哺乳动物中枢神经系统神经元在损伤后往往无法成功恢复。就此而言,下丘脑 - 神经垂体束的单侧损伤会导致35日龄大鼠视上核(SON)未受损轴突出现侧支芽生,但125日龄大鼠则不会。因此,似乎SON内存在与年龄相关的变化,这使得老年大鼠在轴突切断后无法恢复。我们假设轴突重组的内在能力可能部分取决于细胞粘附分子中与年龄相关的变化,这些变化允许SON中正常的星形胶质细胞 - 神经元相互作用。支持我们假设的是,大量报告表明,在轴突生长停止时,神经元中的Thy - 1会增加。因此,我们使用蛋白质印迹分析比较了35日龄和125日龄SON中Thy - 1以及与Thy - 1相互作用的整合素亚基α - v(α)、β - 3(ß)和β - 5(ß)的蛋白质水平。我们的结果表明,与35日龄的SON相比,125日龄的SON中Thy - 1蛋白明显更多,但整合素亚基的蛋白质水平没有变化。此外,我们将Thy - 1、α整合素、ß整合素和ß整合素免疫反应性定位到SON中的神经元和星形胶质细胞。总之,我们的结果表明,SON中Thy - 1蛋白水平随年龄增长而增加,这可能导致一种环境,阻止125日龄大鼠SON中的轴突侧支芽生。