Abstract:

Objective To explore the mechanism of nervous system injury in Wilson's disease by analysis of cell apoptosis, determination of concentrations of Ca and Cu and detection of expression of ATP7A in different parts of brain tissues of Atp7btx-J mice. Methods The tissues of cerebral cortex, cerebellum, basal ganglia and hippocampus of Atp7btx-J mice aged 20 weeks were isolated, the cell apoptosis was analyzed after Hoechst staining, the concentrations of Ca and Cu were determined by inductively coupled plasma mass spectrometry, and the expression of ATP7A mRNA in different parts was detected by Real-Time PCR. Results Compared with wild type mice, the cell apoptosis in cerebellum and basal ganglia of homozygous mice was most significant (P<0.05). The concentrations of Ca and Cu in cerebellum, basal ganglia and hippocampus of homozygous mice were significantly higher than those of wild type mice (P<0.01). The expression of ATP7A mRNA in different parts of brains of homozygous mice was lower than that of wild type mice, and there were significant differences between the expression of ATP7A mRNA in basal ganglia and that in cerebellum (P<0.05). Conclusion Many factors contribute to the nervous system damage in Wilson's disease. The abnormal accumulation of Cu in specific parts of the brain is the initiating factor, Ca mediated apoptosis is one of the important factors, and the incompetency of ATP7A in Cu discharge may exacerbate the nervous system damage in Wilson's disease.

Key words: Wilson's disease, Atp7btx-J mouse, brain