Htain W W, Leong S K, Ling E A
Department of Anatomy, Faculty of Medicine, National University of Singapore.
Glia. 1995 Sep;15(1):11-21. doi: 10.1002/glia.440150103.
A qualitative and quantitative light and electron microscopic analysis of the glial cells in the supraventricular part of the corpus callosum of the neonatal and adult homozygous athymic nude (nu/nu) and normal BALB/c (+/+) mice was carried out to determine the possible contribution of nude gene mutation to glial cell development. Quantitative cell counts using toluidine blue stained serial callosal sections of 0.5 micron thickness showed that the overall glial cell population was significantly reduced in both neonatal and adult athymic mice. The number of glioblasts, astrocytes and microglia of 5-day-old athymic mouse was reduced by 10%, 27%, and 39%, respectively, when compared to the 5-day-old normal mouse. The frequency of necrotic cells in the neonatal athymic mouse increased by 70% when compared with the normal mouse. In the 13-week-old adult athymic mouse, the number of oligodendrocytes, astrocytes, and microglia decreased by 19%, 31%, and 33%, respectively, when compared to normal mouse. There was no significant difference in the area covered by the corpus callosum in 5-day-old and adult nude mice versus the normal ones of corresponding ages. Except for microglia and astrocytes, the ultrastructural features of the other glial cell types in both strains were comparable. Most of the microglial cells of the neonatal normal mouse were round and were selectively marked by Mac-1 monoclonal antibody at their plasma membrane. The immunoreactivity appeared to be more intense in the normal than the athymic mouse, suggesting a down regulation of CR3 receptors and reduced phagocytic activity of this cell type in the athymic mouse. It is proposed that the increased number of necrotic cells in the neonatal athymic mouse may be attributed to the delay in the removal of dead cells normally phagocytosed by microglia. The microglia in both strains of mouse showed comparable lectin staining intensity at the plasma membrane, indicating that their glycoprotein binding receptors to lectin remained unchanged. Some astrocytes in the adult athymic mice showed hypertrophy. The reduced number of glial cells may be the direct result of genetic mutation or consequential to the lack of certain trophic factors arising from the genetic mutation. Thus, the reduction of microglial cells in both neonatal and adult athymic mice may be due to the lack of thymic hormones which, together with lymphokines have been shown to affect the maturation of bone marrow-derived cells including monocytes, the putative precursor cells of microglia. The reduction in the number of glioblasts and astrocytes may be attributed to the diminution of T lymphocytes or consequential to the reduction of microglia which are known to secrete interleukin-1 that would influence gliogenesis and produce specific growth factors for promoting astrocyte proliferation. Last, as interaction exists between astrocytes and oligodendrocytes, the products of astrocytes may affect the development of oligodendrocytes and vice vasa. The present findings point to a relation between glial cell development and immune network system.
对新生和成年纯合无胸腺裸鼠（nu/nu）及正常BALB/c（+/+）小鼠胼胝体室上部分的神经胶质细胞进行了定性和定量的光镜及电镜分析，以确定裸基因突变对神经胶质细胞发育的可能影响。使用厚度为0.5微米的甲苯胺蓝染色胼胝体连续切片进行定量细胞计数，结果显示新生和成年无胸腺小鼠的神经胶质细胞总数均显著减少。与5日龄正常小鼠相比，5日龄无胸腺小鼠的成胶质细胞、星形胶质细胞和小胶质细胞数量分别减少了10%、27%和39%。与正常小鼠相比，新生无胸腺小鼠中坏死细胞的频率增加了70%。在13周龄的成年无胸腺小鼠中，与正常小鼠相比，少突胶质细胞、星形胶质细胞和小胶质细胞数量分别减少了19%、31%和33%。5日龄和成年裸鼠胼胝体覆盖的面积与相应年龄的正常小鼠相比无显著差异。除小胶质细胞和星形胶质细胞外，两种品系中其他神经胶质细胞类型的超微结构特征具有可比性。新生正常小鼠的大多数小胶质细胞呈圆形，其质膜上可被Mac-1单克隆抗体选择性标记。正常小鼠中的免疫反应性似乎比无胸腺小鼠更强，这表明无胸腺小鼠中CR3受体下调，该细胞类型的吞噬活性降低。据推测，新生无胸腺小鼠中坏死细胞数量增加可能归因于小胶质细胞正常吞噬的死细胞清除延迟。两种品系小鼠的小胶质细胞质膜上凝集素染色强度相当，表明它们与凝集素的糖蛋白结合受体保持不变。成年无胸腺小鼠中的一些星形胶质细胞出现肥大。神经胶质细胞数量减少可能是基因突变的直接结果，或者是基因突变导致某些营养因子缺乏的后果。因此，新生和成年无胸腺小鼠中小胶质细胞数量减少可能是由于缺乏胸腺激素，胸腺激素与淋巴因子一起已被证明会影响包括单核细胞（小胶质细胞的假定前体细胞）在内的骨髓来源细胞的成熟。成胶质细胞和星形胶质细胞数量减少可能归因于T淋巴细胞减少，或者是由于小胶质细胞减少的结果，已知小胶质细胞分泌白细胞介素-1，白细胞介素-1会影响神经胶质生成并产生促进星形胶质细胞增殖的特定生长因子。最后，由于星形胶质细胞和少突胶质细胞之间存在相互作用，星形胶质细胞的产物可能影响少突胶质细胞的发育，反之亦然。目前的研究结果表明神经胶质细胞发育与免疫网络系统之间存在关联。
