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- Title
The role of parvalbumin and calbindin D28k in experimental scrapie.
- Authors
Voigtländer, T.; Unterberger, U.; Guentchev, M.; Schwaller, B.; Celio, M. R.; Meyer, M.; Budka, H.
- Abstract
Aims: Prion diseases are generally characterized by pronounced neuronal loss. In particular, a subpopulation of inhibitory neurones, characterized by the expression of the calcium-binding protein parvalbumin (PV), is selectively destroyed early in the course of human and experimental prion diseases. By contrast, nerve cells expressing calbindin D28k (CB), another calcium-binding protein, as well as PV/CB coexpressing Purkinje cells, are well preserved. Methods: To evaluate, if PV and CB may directly contribute to neuronal vulnerability or resistance against nerve cell death, respectively, we inoculated PV- and CB-deficient mice, and corresponding controls, with 139A scrapie and compared them with regard to incubation times and histological lesion profiles. Results: While survival times were slightly but significantly diminished in CB–/–, but not PV–/– mice, scrapie lesion profiles did not differ between knockout mice and controls. There was a highly significant and selective loss of isolectin B4-decorated perineuronal nets (which specifically demarcate the extracellular matrix surrounding the ‘PV-expressing’ subpopulation of cortical interneurones) in scrapie inoculated PV+/+, as well as PV–/– mice. Purkinje cell numbers were not different in CB+/+ and CB–/– mice. Conclusions: Our results suggest that PV expression is a surrogate marker for neurones highly vulnerable in prion diseases, but that the death of these neurones is unrelated to PV expression and thus based on a still unknown pathomechanism. Further studies including the inoculation of mice ectopically (over)expressing CB are necessary to determine whether the shortened survival of CB–/– mice is indeed due to a neuroprotective effect of this molecule.
- Subjects
PRION diseases; NEURONS; CELLS; PRECANCEROUS conditions; CALCIUM-binding proteins; CELL death; PURKINJE cells; MOLECULES; PROTEINS; MICE
- Publication
Neuropathology & Applied Neurobiology, 2008, Vol 34, Issue 4, p435
- ISSN
0305-1846
- Publication type
Article
- DOI
10.1111/j.1365-2990.2007.00902.x