Jantaratnotai Nattinee, Ryu Jae K, Kim Seung U, McLarnon James G
Department of Pharmacology, The University of British Columbia, 2176 Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3.
Neuroreport. 2003 Aug 6;14(11):1429-33. doi: 10.1097/00001756-200308060-00005.
The effects of stereotaxic injection of amyloid beta-peptide (Abeta1-42) into rat brain to induce white matter damage have been studied. Administration of 1 nmol Abeta1-42 into corpus callosum resulted in considerable damage to axons as evidenced by the loss of neurofilament-immunoreactive (NF-ir) fibers 6 h and 3 and 7 days post-injection. Significant damage was also evident to myelin (using Luxol fast blue myelin staining) and oligodendrocytes (using CC1 immunocytochemistry); in the latter case marked caspase-3 immunoreactivity was evident in oligodendrocytes. Additionally, the numbers of GFAP-ir astrocytes and OX-42/OX-6-ir microglia were markedly increased following Abeta1-42 injection. These results suggest that Abeta plays an important pathophysiological role in white matter damage and that inflammatory responses may contribute to Abeta-induced demyelination and oligodendrocyte injury in corpus callosum. Loss of function of cells in corpus callosum could provide a potential new model for the study of white matter damage in Alzheimer's disease.
已对向大鼠脑内立体定向注射β-淀粉样肽（Aβ1-42）以诱导白质损伤的效应进行了研究。向胼胝体注射1 nmol Aβ1-42导致轴突受到相当程度的损伤，注射后6小时以及3天和7天神经丝免疫反应性（NF-ir）纤维的丧失证明了这一点。髓鞘（使用Luxol固蓝髓鞘染色）和少突胶质细胞（使用CC1免疫细胞化学）也出现了明显损伤；在后一种情况下，少突胶质细胞中可见明显的半胱天冬酶-3免疫反应性。此外，注射Aβ1-42后，GFAP-ir星形胶质细胞和OX-42/OX-6-ir小胶质细胞的数量显著增加。这些结果表明，Aβ在白质损伤中起重要的病理生理作用，并且炎症反应可能导致Aβ诱导的胼胝体脱髓鞘和少突胶质细胞损伤。胼胝体细胞功能丧失可为研究阿尔茨海默病中的白质损伤提供一个潜在的新模型。
