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Abstract

 
Abstract No.:C-A3005
Country:Canada
  
Title:FROM PATTERNED GENE EXPRESSION TO MRI STRIPES IN THE ANTERIOR ZONE OF THE HUMAN CEREBELLUM
  
Authors/Affiliations:1 Hassan Marzban; 1 Kamal Sahi*; 1 Vimal Prajapati; 1 S-H Chung; 2 N.J. Scott; 3 J.F Dunn; 1 R. Hawkes;
1 Department of Cell Biology & Anatomy, Hotchkiss Brain Institute, GDRG, Faculty of Medicine, University of Calgary, AB, Canada; 2 Dept of Diagnostic Imaging, Foothills Medical Centre, Calgary, AB, Canada; 3 Experimental Imaging Centre, Dept. of Radiology, Faculty of Medicine, University of Calgary, AB, Canada
  
Content:Introduction: The cerebellum is histologically uniform and the cytoarchitecture is similar through all lobules of the vermis and hemispheres. Underlying the relatively simple cellular organization of the cerebellum, however, is a complex arrangement of parasagittal stripes and transverse zones that is revealed by using physiological mapping, anatomical tracing, mutational analysis, molecular markers and cell degeneration. The primary organizer seems to be the Purkinje cell. The most extensively studied marker of cerebellar compartmentation is the antigen zebrin II, which is expressed strongly in subsets of Purkinje cells and form a highly reproducible array of parasagittal stripes. Subsequent studies have shown zebrin II to be an epitope on the respiratory isoenzyme aldolase C. The functional significance of differential zebrin II/aldolase C expression is unknown, but it is clear that it reflects intrinsic differences between different Purkinje cell subsets rather than being a secondary response to patterns of usage. In the present study we compare zebrin II expression in the postmortem human anterior lobe vermis with MRI data from the same region. The results show an alternating pattern of high and low zebrin II expression, which has a clear correlate in the MRI images.

Materials and Methods: Adult wild type mice and Homozygous BALB/c npcnih mice were obtained from Charles River Laboratories and Jackson Laboratories, respectively. Human cerebellum samples for immunohistochemical study were obtained from cadavers of adult human at the gross neuroanatomy laboratory courses. Peroxidase immunohistochemistry was carried out on cerebellar sections and whole mount. MR image acquisition on a human cerebellum was performed at 3-Tesla (Signa; GE Medical Systems) at Imaging Facility Centre of Foothill Hospital, Calgary.

Results: ZII immnohistochemistry of the adult mice cerebellum is parasagittal stripes in AZ. CaBP immunostaining of the Niemann–Pick type C mutant mice is shown PCs degeneration is patterned stripes that correspond to the ZII immunopositive stripes. ZII is expressed strongly in PCs of the human cerebellum. Subset of PCs in human cerebellum is strongly expressed ZII and in other subset it is expressed weakly or nothing at all. Axial T2-weighted image of the human brain (T2w, TR/TE=4090/109ms) reveals an alternate intensity pattern of stripes in the anterior zone of the cerebellum that showing the MR stripes may correspond to the ZII patterned stripe.

Conclusion: This abstract shows that the human cerebellum expresses the Purkinje cell antigen zebrin II. Two populations of Purkinje cells can be identified: with high (P+) and low (P-) expression Levels. The P+ and P- Purkinje cells are arranged in parasagittal stripes in the anterior zone. These stripes are not visible with regular histology. MRI of the anterior cerebellum reveals a similar stripe array to that seen with anti-zebrin II immunocytochemistry. This striping is currently only visualized with immunohistochemistry and with MRI. There is a positive correlation between the molecular target and the MRI. This unique application of MRI will be useful for studying cerebellar abnormalities during development and disease progression. The underlying cellular mechanism for the contrast remains to be determined.



  
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