Department of Physiology and Immunology, Medical Faculty, University of Rijeka, Rijeka, Croatia.
Histol Histopathol. 2011 Feb;26(2):233-45. doi: 10.14670/HH-26.233.
To elucidate the role of metallothioneins (MTs) in the pathomechanisms of autoimmune CNS disorders we estimated the expression of MTs I+II and the tissue concentrations of Zn²+ and Cu²+ in the brain, spinal cord (SC) and in the liver during the periods of attacks and remissions in chronic relapsing experimental autoimmune encephalomyelitis (CR-EAE). Disease was induced in the genetically susceptible Dark Agouti (DA) rats by subcutaneous injection of bovine brain homogenate in CFA. Control rats were treated with CFA. The data, obtained by clinical assessment, immunohistochemistry and inductivity coupled plasma spectrometry, have shown that during the first attack (on the 12th day) MTs I+II were markedly upregulated in subarachnoid regions and perivascular space on astrocytes, microglia and on spinal neurons. Simultaneously, the concentrations of zinc in the SC and zinc and copper in the liver have found to be increased. During the second attack (on the 22nd day) a new overexpression of MTs was found in the cerebellum, in sulcus hippocampi, in spinal neurons and particularly in hepatocytes around the central vein. Concomitantly, in the brain and SC the concentration of copper increased. The data point to a neuroprotective role of MTs and to an important regulatory role of essential metals and hepatic MTs in the pathogenesis of CR-EAE.
为了阐明金属硫蛋白（MTs）在自身免疫性中枢神经系统疾病发病机制中的作用，我们在慢性复发性实验性自身免疫性脑脊髓炎（CR-EAE）的发作和缓解期，估计了 MTs I+II 的表达以及脑、脊髓（SC）和肝脏中的 Zn²+和 Cu²+组织浓度。通过在 CFA 中皮下注射牛脑匀浆，在遗传易感的 Dark Agouti（DA）大鼠中诱导疾病。对照大鼠用 CFA 治疗。通过临床评估、免疫组织化学和电感耦合等离子体质谱获得的数据表明，在第一次发作（第 12 天）期间，蛛网膜下腔区域和血管周围空间的星形胶质细胞、小胶质细胞和脊髓神经元上的 MTs I+II 明显上调。同时，发现 SC 中的锌浓度以及肝脏中的锌和铜浓度增加。在第二次发作（第 22 天）时，小脑、海马沟、脊髓神经元，特别是中央静脉周围的肝细胞中发现 MTs 的新过度表达。同时，脑和 SC 中的铜浓度增加。这些数据表明 MTs 具有神经保护作用，并且必需金属和肝脏 MTs 在 CR-EAE 的发病机制中具有重要的调节作用。
