Gonzalez M L, Silver J
Department of Neurosciences, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106-4975.
J Neurosci. 1994 Oct;14(10):6121-31. doi: 10.1523/JNEUROSCI.14-10-06121.1994.
It has been suggested that an inhibitory ECM containing chondroitin-6-sulfate proteoglycan (C-6S-PG) and tenascin (TN), which appears homogeneously in the core of the OB following afferent fiber arrival, helps position ingrowing olfactory axons in the prospective glomerular layer (GL) (Gonzalez and Silver, 1992; Gonzalez et al., 1993). Later, a similar ECM associated with astrocytes envelopes axonal glomeruli in rings, suggesting that axons may control the precise ECM patterning. The question remains whether formation of the matrix ring pattern around each axonal glomerulus is an intrinsic property of the matrix-producing cells or a response to developing axons. To determine if the organization of glial associated matrix in the OB was dependent on the presence of axons, we studied the effect of unilateral injection of a neurotoxin into the olfactory epithelium of postnatal rats. Using olfactory marker protein (OMP), beta-tubulin (TUJ1) antibodies, and Nissl staining, we found that at 5 and 10 d following neurotoxin administration the number of glomeruli decreased by an average of 77.0% in the injected side. At the same time, we observed that the TN/C-6S-PG rings and periglomerular cells were present only around the remaining small number of glomeruli. Elsewhere, ECM expression and the periglomerular cell configuration were more disorganized in the GL. The pattern of glial fibrillary acidic protein (GFAP) did not change significantly. We found that OMP staining, beta-tubulin immunoreactivity, and periglomerular cells reformed in a glomerular-like pattern as the olfactory axons reformed by 20 d. As the glomeruli-shaped collection of axon terminals reappeared, TN/C-6S-PG immunoreactivity also reoccurred in rings around the new axon bundles. Again, at this later stage, the expression of GFAP was similar in both sides. In our previous study (Gonzalez et al., 1993), we suggested that the initial gross positioning of glomeruli may be controlled by the overall positioning of TN/C-6S-PG. In the present study, we suggest that the formation of TN/C-6S-PG in the precise ring pattern around glomeruli appears to be dependent upon the presence of bundled olfactory axons. Various mechanisms are discussed that may explain the dynamic change in ECM expression that occurs inside the glomerulus after the neurotoxin treatment.
有人提出,一种含有硫酸软骨素-6-硫酸盐蛋白聚糖(C-6S-PG)和腱生蛋白(TN)的抑制性细胞外基质,在传入纤维到达后在嗅球核心均匀出现,有助于将生长中的嗅觉轴突定位在前瞻性肾小球层(GL)中(冈萨雷斯和西尔弗,1992;冈萨雷斯等人,1993)。后来,一种与星形胶质细胞相关的类似细胞外基质以环状包裹轴突肾小球,这表明轴突可能控制精确的细胞外基质模式形成。问题仍然是,围绕每个轴突肾小球形成基质环模式是基质产生细胞的固有特性,还是对发育中轴突的反应。为了确定嗅球中胶质细胞相关基质的组织是否依赖于轴突的存在,我们研究了向新生大鼠嗅上皮单侧注射神经毒素的影响。使用嗅觉标记蛋白(OMP)、β-微管蛋白(TUJ1)抗体和尼氏染色,我们发现,在给予神经毒素后5天和10天,注射侧的肾小球数量平均减少了77.0%。与此同时,我们观察到TN/C-6S-PG环和肾小球周围细胞仅存在于剩余的少数肾小球周围。在其他地方,GL中的细胞外基质表达和肾小球周围细胞构型更加紊乱。胶质纤维酸性蛋白(GFAP)的模式没有明显变化。我们发现,随着嗅觉轴突在20天时重新形成,OMP染色、β-微管蛋白免疫反应性和肾小球周围细胞以类似肾小球的模式重新形成。随着轴突终末的肾小球状聚集重新出现,TN/C-6S-PG免疫反应性也在新轴突束周围的环中再次出现。同样,在这个后期阶段,两侧GFAP的表达相似。在我们之前的研究(冈萨雷斯等人,1993)中,我们提出肾小球的初始大致定位可能由TN/C-6S-PG的整体定位控制。在本研究中,我们提出,围绕肾小球形成精确环模式的TN/C-6S-PG似乎依赖于成束的嗅觉轴突的存在。讨论了各种可能解释神经毒素处理后肾小球内细胞外基质表达动态变化的机制。