ABNORMAL EXPRESSION OF EMBRYONIC NEURAL CELL-ADHESION MOLECULE (N-CAM) IN THE DEVELOPING MOUSE CEREBELLUM AFTER NEONATAL ADMINISTRATION OF CYTOSINE-ARABINOSIDE

We have previously found that neonatal administration of cytosine arabinoside (Ara-C) induces cerebellar malformation, including arrest of granule cell migration and destruction of glial palisade. In the present study, the expression of neural cell adhesion molecule (N-CAM) and its distribution were examined in the mouse malformed cerebellum induced by neonatal Ara-C administration. Western blot analysis demonstrated that, in the control group, the embryonic form of N-CAM (E-N-CAM) was expressed in the 7-day-old mouse (P7) cerebellum, but not in the P14 cerebellum which exhibited only the adult form of N-CAM (A-N-CAM). On the other hand, E-N-CAM was expressed in the Ara-C treated cerebellum not only at P7 but also at P14. Immunohistochemical studies revealed that E-N-CAM was observed in the area below the external granular layer (EGL) of the P7 cerebellum in both the control and Ara-C treated mice. In contrast, E-N-CAM immunoreactivity was found in the arrested EGL cells in the Ara-C treated cerebellum of P14 mice but not in the age-matched controls. Therefore, E-N-CAM was aberrantly expressed in the arrested EGL at P14. From the present and previous findings, it was speculated that the aberrant expression of E-N-CAM in the arrested EGL cells is attributed to abnormal cellular interactions, probably arrested EGL cell-to-Bergmann glia.