Morgan Kathleen L, Chalovich Elisabeth Mole, Strachan Gordon D, Otis Linda L, Jordan-Sciutto Kelly L
Department of Pathology, University of Pennsylvania, School of Dental Medicine, 240 S. 40th St., Rm 312 Levy Bldg, Philadelphia, PA 19104-6030, USA.
Neurosci Lett. 2005 Jul 15;382(3):259-64. doi: 10.1016/j.neulet.2005.03.044. Epub 2005 Apr 14.
The E2F1 transcriptional regulator has been shown to exhibit altered expression and localization in HIVE and SIVE. However, other E2F family members are expressed in mature neurons and participate in neuronal differentiation. In an in vitro model of neuronal differentiation, E2F4 protein levels have been shown to increase. Further reduction in E2F4 leads to loss of neurites in this model. Neuritic damage and loss are also seen in progression of HIVE and SIVE. To determine if changes in E2F4 may contribute to altered neuronal morphology and survival, we assessed E2F4 immunostaining in caudate and mid-frontal cortex from SIVE macaques and non-encephalitic controls. We found that E2F4 was expressed in neurons and localized to nuclei in both SIVE and non-encephalitic controls. Quantification of E2F4 fluorescence intensity indicated that there was an overall decrease in E2F4 in caudate of SIVE macaques as compared to non-encephalitic controls, which correlated with a decrease in the neuronal phenotypic marker, MAP2. In contrast, we observed a slight increase in E2F4 in mid-frontal cortex of SIVE despite a significant decrease in MAP2. When E2F4 is normalized to MAP2, we found an increase in E2F4 fluorescence intensity per MAP2 in SIVE mid-frontal cortex. These findings suggest changes in E2F4 may be contributing to altered neuronal morphology or survival in SIVE.
E2F1转录调节因子已被证明在人免疫缺陷病毒脑炎（HIVE）和严重免疫缺陷病毒脑炎（SIVE）中表达和定位发生改变。然而，其他E2F家族成员在成熟神经元中表达并参与神经元分化。在神经元分化的体外模型中，E2F4蛋白水平已被证明会增加。在该模型中，E2F4的进一步减少会导致神经突丧失。在HIVE和SIVE的进展过程中也可见神经突损伤和丧失。为了确定E2F4的变化是否可能导致神经元形态和存活的改变，我们评估了来自SIVE猕猴和非脑炎对照的尾状核和额中皮质中的E2F4免疫染色。我们发现，在SIVE和非脑炎对照中，E2F4均在神经元中表达并定位于细胞核。E2F4荧光强度的定量分析表明，与非脑炎对照相比，SIVE猕猴尾状核中的E2F4总体减少，这与神经元表型标志物微管相关蛋白2（MAP2）的减少相关。相反，尽管MAP2显著减少，但我们观察到SIVE额中皮质中的E2F4略有增加。当E2F4与MAP2进行归一化时，我们发现SIVE额中皮质中每MAP2的E2F4荧光强度增加。这些发现表明，E2F4的变化可能导致SIVE中神经元形态或存活的改变。
