Ayoub Albert E, Salm A K
Department of Neurobiology and Anatomy, West Virginia University School of Medicine, Morgantown, West Virginia 26506-9128, USA.
J Neurosci. 2003 Aug 27;23(21):7759-66. doi: 10.1523/JNEUROSCI.23-21-07759.2003.
Microglia are the immune cells of the CNS. In the normal adult mammalian brain, the majority of these cells is quiescent and exhibits a ramified morphology. Microglia are perhaps best known for their swift transformation to an activated ameboid morphology in response to pathological insults. Here we have observed the responsiveness of these cells to events surrounding the normal activation of neurosecretory neurons in the hypothalamic supraoptic nucleus (SON), a well studied model of structural plasticity in the CNS. Neurons in the SON were activated by substituting 2% saline for drinking water. Brain sections were collected from four experimental groups [controls (C), 2 d-dehydrated (2D), 7 d-dehydrated (D7), and 7 d-dehydrated/21 d-rehydrated animals (R21)] and stained with Isolectin-B4-HRP to visualize microglial cells. Based on morphological criteria, we quantified ramified, hypertrophied, and ameboid microglia using unbiased stereological techniques. Statistical analyses showed significant increases in the number of hypertrophied microglia in the D2 and D7 groups. Moreover, there was a significant increase in the number of ameboid microglia in the D7 group. No changes were seen across conditions in the number of ramified cells, nor did we observe any significant phenotypic changes in a control area of the cingulate gyrus. Hence, increased morphological diversity of microglia was found specifically in the SON and was reversible with the cessation of stimulation. These results indicate that phenotypic plasticity of microglia may be a feature of the normal structural remodeling that accompanies neuronal activation in addition to the activation that accompanies brain pathology.
小胶质细胞是中枢神经系统的免疫细胞。在正常成年哺乳动物大脑中,这些细胞中的大多数处于静止状态,并呈现出分支状形态。小胶质细胞可能最为人所知的是,它们会在受到病理损伤时迅速转变为活化的阿米巴样形态。在这里,我们观察了这些细胞对下丘脑视上核(SON)中神经分泌神经元正常激活周围事件的反应,SON是中枢神经系统中一个经过充分研究的结构可塑性模型。通过用2%盐水替代饮用水来激活SON中的神经元。从四个实验组[对照组(C)、2天脱水组(2D)、7天脱水组(D7)和7天脱水/21天再水化动物组(R21)]收集脑切片,并用异凝集素-B4-HRP染色以可视化小胶质细胞。基于形态学标准,我们使用无偏立体学技术对分支状、肥大状和阿米巴样小胶质细胞进行了量化。统计分析表明,D2组和D7组中肥大状小胶质细胞的数量显著增加。此外,D7组中阿米巴样小胶质细胞的数量也显著增加。在不同条件下,分支状细胞的数量没有变化,我们在扣带回的一个对照区域也未观察到任何显著的表型变化。因此,小胶质细胞形态多样性的增加在SON中是特异性发现的,并且随着刺激的停止是可逆的。这些结果表明,小胶质细胞的表型可塑性可能是伴随神经元激活的正常结构重塑的一个特征,而不仅仅是伴随脑病理的激活。