Vela J M, Hidalgo J, González B, Castellano B
Department of Cell Biology and Physiology, Faculty of Medicine, Autonomous University of Barcelona, Bellaterra, Spain.
Brain Res. 1997 Sep 5;767(2):345-55. doi: 10.1016/s0006-8993(97)00628-8.
Jimpy is a shortened life-span murine mutant whose genetic disorder results in severe pathological alterations in the CNS, including hypomyelination, oligodendrocyte death and strong astroglial and microglial reaction. The knowledge of metallothionein (MT) regulation in the CNS and especially of MT presence in specific glial cell types under pathological conditions is scarce. In the present study, immunocytochemical detection of MT-I + II has been performed in spinal cord sections from 10-12- and 20-22-day-old jimpy and normal animals. The identification of MT-positive glial cells was achieved through double labeling combining MT immunocytochemistry and selective markers for oligodendrocytes, astrocytes and microglia. MT was found in glial cells and was present in the spinal cord of jimpy and normal mice at both ages, but there were remarkable differences in MT expression and in the nature of MT-positive glial cells depending on the type of mouse. The number of MT-positive cells was higher in jimpy than in normal spinal cords. This was apparent in all spinal cord areas, although it was more pronounced in white than in the gray matter and at 20-22 days than at 10-12 days. The mean number of MT-positive glia in the jimpy white matter was 1.9-fold (10-12 days) and 2.4-fold (20-22 days) higher than in the normal one. Astrocytes were the only parenchymal glial cells that were positively identified as MT-producing cells in normal animals. Interestingly, MT in the jimpy spinal cord was localized not only in astrocytes but also in microglial cells. The occurrence of MT induction in relation to reactive astrocytes and microglia, and its role in neuropathological conditions is discussed.
Jimpy是一种寿命缩短的小鼠突变体,其遗传疾病导致中枢神经系统出现严重的病理改变,包括髓鞘形成不足、少突胶质细胞死亡以及强烈的星形胶质细胞和小胶质细胞反应。关于中枢神经系统中金属硫蛋白(MT)的调节,尤其是在病理条件下特定胶质细胞类型中MT的存在情况,目前了解甚少。在本研究中,对10 - 12日龄和20 - 22日龄的Jimpy小鼠和正常动物的脊髓切片进行了MT - I + II的免疫细胞化学检测。通过将MT免疫细胞化学与少突胶质细胞、星形胶质细胞和小胶质细胞的选择性标记物相结合的双重标记,实现了对MT阳性胶质细胞的鉴定。在胶质细胞中发现了MT,并且在两个年龄段的Jimpy小鼠和正常小鼠的脊髓中都有MT存在,但根据小鼠类型的不同,MT表达和MT阳性胶质细胞的性质存在显著差异。Jimpy小鼠中MT阳性细胞的数量高于正常脊髓。这在所有脊髓区域都很明显,尽管在白质中比在灰质中更明显,在20 - 22日龄时比在10 - 12日龄时更明显。Jimpy小鼠白质中MT阳性胶质细胞的平均数量比正常小鼠高1.9倍(10 - 12日龄)和2.4倍(20 - 22日龄)。在正常动物中,星形胶质细胞是唯一被明确鉴定为产生MT的实质胶质细胞。有趣的是,Jimpy小鼠脊髓中的MT不仅定位于星形胶质细胞,还定位于小胶质细胞。本文讨论了与反应性星形胶质细胞和小胶质细胞相关的MT诱导的发生情况及其在神经病理条件中的作用。