Department for General Physiology and Biophysics, Faculty of Biology, University of Belgrade, Belgrade, Studentski trg 3, 11001 Belgrade, Serbia; Department of Molecular Biology and Endocrinology, Vinča Institute of Nuclear Sciences, University of Belgrade, Mike Petrovića Alasa 12-14, 11001 Belgrade, Serbia.
Department of Molecular Biology and Endocrinology, Vinča Institute of Nuclear Sciences, University of Belgrade, Mike Petrovića Alasa 12-14, 11001 Belgrade, Serbia.
Neuroscience. 2019 Dec 15;423:38-54. doi: 10.1016/j.neuroscience.2019.10.022. Epub 2019 Nov 1.
Astrocytes comprise a heterogenic group of glial cells, which perform homeostatic functions in the central nervous system. These cells react to all kind of insults by changing the morphology and function that result in a transition from the quiescent to a reactive phenotype. Trimethyltin (TMT) intoxication, which reproduces pathological events in the hippocampus similar to those associated with seizures and cognitive decline, has been proven as a useful model for studying responses of the glial cells to neurodegeneration. In the present study, we have explored morphological varieties of astrocytes in the hippocampal subregions of ovariectomized female rats exposed to TMT. We have demonstrated an early loss of neurons in CA1 and DG subfields. Distinct morphotypes of protoplasmic astrocytes observed in CA1/CA3 and the hilus of control animals developed different responses to TMT intoxication, as assessed by GFAP-immunohistochemistry. In CA1 subregion, GFAP astrocytes preserved their domain organization and responded with typical hypertrophy, while the hilar GFAP astrocytes developed atrophy-like phenotype and increased expression of vimentin and nestin 7 days after the exposure. Both reactive and atrophied-like astrocytes expressed Kir4.1 in CA1/CA3 and the hilus of DG, respectively, indicating that these cells did not change their potential for normal activity at this time point of pathology. Together, the results demonstrate the persistence of two protoplasmic morphotypes of astrocytes, with distinct appearance, function, and fate after TMT-induced neurodegeneration, suggesting their pleiotropic roles in the hippocampal response to neurodegeneration.
星形胶质细胞是一类异质性的神经胶质细胞，在中枢神经系统中发挥着维持内环境稳定的功能。这些细胞会对外界的各种刺激做出反应，改变形态和功能，从而从静息状态转变为反应性表型。三甲基锡（TMT）中毒可以复制海马体中的病理事件，这些事件类似于与癫痫发作和认知能力下降相关的事件，已被证明是研究神经胶质细胞对神经退行性变反应的有用模型。在本研究中，我们探索了暴露于 TMT 的去卵巢雌性大鼠海马亚区中星形胶质细胞的形态变化。我们已经证明 CA1 和 DG 亚区中的神经元发生了早期丢失。在对照动物的 CA1/CA3 和齿状回的门区观察到的原浆型星形胶质细胞的不同形态类型对 TMT 中毒表现出不同的反应，这可以通过 GFAP-免疫组织化学评估。在 CA1 亚区，GFAP 星形胶质细胞保留了它们的域组织，并表现出典型的肥大反应，而门区的 GFAP 星形胶质细胞则发展出类似萎缩的表型，并增加了波形蛋白和巢蛋白的表达，在暴露后 7 天。反应性和萎缩样星形胶质细胞在 CA1/CA3 和 DG 门区分别表达 Kir4.1，表明这些细胞在病理发生的这个时间点没有改变它们的正常活性潜力。总之，这些结果表明，在 TMT 诱导的神经退行性变后，两种原浆型星形胶质细胞形态仍然存在，具有不同的外观、功能和命运，这表明它们在海马体对神经退行性变的反应中具有多效性作用。
