Analysis of aberrant neuronal migrations in the hereditary cerebellar vermis defect (CVD) rat using bromodeoxyuridine immunohistochemistry

• Published in: Acta neuropathologica Vol. 95; no. 2; pp. 143 - 148
• Main Authors: KUWAMURA, M, SHIROTA, A, YAMATE, J, KOTANI, T, SAKUMA, S
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.02.1998; Springer Nature B.V
• Subjects: Aging; Animals; Animals, Newborn; Biological and medical sciences; Blood vessels; Bromodeoxyuridine; Calbindin; Cell Aggregation; Cell Movement; Cerebellar Diseases - genetics; Cerebellar Diseases - pathology; Cerebellar Diseases - physiopathology; Cerebellopontine Angle - abnormalities; Cerebellopontine Angle - growth & development; Cerebellopontine Angle - pathology; Cerebellum; Cerebellum - abnormalities; Cerebellum - growth & development; Cerebellum - pathology; Defects; Dysplasia; Embryos; Granule cells; Immunohistochemistry; Lamination; Malformations of the nervous system; Medical sciences; Neurology; Neurons - pathology; Neurons - physiology; Pons; Purkinje cells; Purkinje Cells - pathology; Purkinje Cells - physiology; Rats; Rats, Mutant Strains; Immunohistochemistry; Rat; Pathogenesis; Migration; Postnatal development; Cerebellar disease; Lissencephaly; Embryonic development; Nervous system diseases; Dysplasia; Pathophysiology; Histological labelling; Rodentia; Cerebral disorder; Genetic disease; Pathology; Vermis; Vertebrata; Mammalia; Neuron; Broxuridine; Malformation; Follow up study; Animal; Central nervous system disease; Kinetics; Mutation
• ISSN: 0001-6322; 1432-0533
• DOI: 10.1007/s004010050778

The hereditary cerebellar vermis defect rat (CVD) is a new neurological mutant characterized by cerebellar vermis defect and a dysplastic cerebellum, especially in the cerebello-pontine junctions. In this study, the cytokinetics of neuronal migrations in the CVD were analyzed using 5-bromo-2'-deoxyuridine (BrdU) as a labeling marker. From embryonic day 21, the CVD cerebellum was small in size with retarded foliation, but no significant differences were detected in the migration pattern of the BrdU-labeled cells between the unaffected controls and the CVD during the prenatal period. On postnatal day 0 (P0), heterotopic Purkinje cells, demonstrable by calbindin immunohistochemistry, were seen in the dorsal pons of the CVD. From P4, BrdU-positive external granule cells (EGCs), which were labeled by BrdU injection on P2, began to penetrate the pons. From P5, the EGCs aggregated around the blood vessels, leading to a disturbance of the cerebellar lamination both in the cerebello-pontine junctions and in the cerebellar hemispheres. Thereafter, the BrdU-labeled cells in the perivascularly aggregated EGCs migrated radially, and formed internal granular layers around the vessels, indicating an aberrant perivascular migration of the EGCs. These findings suggest that the EGC dislocation was preceded by an aberrant settlement of the Purkinje cells, and that the perivascularly aggregated EGCs resulted in cerebellar dysplasia in the CVD.