Biochemical and Biophysical Research Communications
Role of galectin-3 in prion infections of the CNS
Section snippets
Materials and methods
Mouse strains and scrapie infections. Galectin-3-deficient (galectin-3−/−) mice backcrossed to C57BL/6J have been described [8]. As wild-type controls served a line of C57BL/6J mice derived from crossing of galectin-3+/−-mice. Scrapie strain 139A (courtesy of R.H. Kimberlin, Edinburgh, UK) were employed for the infection experiments. Dilutions of a 10% brain homogenate prepared from scrapie 139A-infected mice were used as the inoculum for intracerebral (i.c.) and intraperitoneal (i.p.)
Results
To determine galectin-3 protein expression in the prion-infected CNS, immunohistochemical analysis was performed at different stages of the disease. As shown in Fig. 1B, galectin-3 expression was already detectable at the asymptomatic stage (i.e. 125 days post infection, (dpi)). At the terminal stage of the disease extensive galectin-3 staining was evident (Fig. 1C). No galectin-3 protein was detectable in brains of mock-infected healthy mice (Fig. 1A).
Given that numerous cell types in the
Discussion
Galectin-3 is a multi-functional protein, which is overexpressed in scrapie-infected brain tissue [13], [14]. We characterized here the scrapie infection of mice deficient for galectin-3 to learn more about a possible role of this protein in chronic neurodegeneration.
Ablation of galectin-3 promoted a significant increase in survival times of up to 3 weeks upon exposure to the scrapie agent (Table 1). The roughly equal effect of the galectin-3-deficiency on survival times upon intracerebral and
Acknowledgments
The authors thank K. Krohn, S. Lichy and E. Westhäuser for excellent technical assistance and Dr. N. Holtkamp for helpful discussions. This work was supported in part by Grant 01KO0515 from the Federal Ministry for Education and Research, Germany, and by funding under the Sixth Research Framework Programme of the European Union, Project AntePrion (LSHB-CT-2006-019090).
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