Localization of the neuronal antigen recognized by anti-Tr antibodies from patients with paraneoplastic cerebellar degeneration and Hodgkin's disease in the rat nervous system.
Patients with paraneoplastic cerebellar degeneration and Hodgkin's disease develop autoantibodies (Tr-Ab) that immunoreact with the cytoplasm of the Purkinje cells and produce a characteristic punctate pattern in the molecular layer of the cerebellum. In the present study, we analyzed the structures of the adult rat cerebellar cortex identified by Tr-Ab and the expression of the antigen recognized by Tr-Ab in the developing rat brain. By laser confocal microscopy and immunoelectron microscopy, Tr-Ab immunoreactivity was found localized in the cytosol and outer surface of the endoplasmic reticulum of the perikarya of neurons of the molecular layer and the cell body and dendrites of Purkinje cells without a particular concentration in dendritic spines. Tr-Ab reactivity was more widespread in the developing rat brain. Tr-Ab labeling of Purkinje cells was already observed at P0 (day of birth). The staining of the molecular layer followed the development of the dendritic tree. The internal and inner level of the external granule cell layer were labeled with Tr-Ab with a dotted pattern that became almost negative by the 2nd postnatal week. The staining probably corresponded to granule cells as suggested by the positive Tr-Ab labeling of cultures of embryonic granule neurons. The present findings suggest that the antigen recognized by Tr-Ab appears early and is widely expressed in the developing rat brain. In the adult cerebellum, the antigen is localized in the cell body and dendrites of the Purkinje cells but is not concentrated in the dendritic spines.
Servei de Neurologia, Hospital Clinic, Universitat de Barcelona, Spain.
F
F
Graus
S H
SH
Gultekin
I
I
Ferrer
J
J
Reiriz
J
J
Alberch
J
J
Dalmau
D000818:Animals; D000941:Antigens / Q000032:analysis*; D001323:Autoantibodies / Q000276:immunology; D002478:Cells, Cultured; D002526:Cerebellar Diseases / Q000378:metabolism / Q000473:pathology*; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology; D006689:Hodgkin Disease / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D016253:Microscopy, Immunoelectron; D009420:Nervous System / Q000378:metabolism / Q000473:pathology*; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000276:immunology*; D010257:Paraneoplastic Syndromes / Q000378:metabolism / Q000473:pathology*; D011689:Purkinje Cells / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
D000941:Antigens; D001323:Autoantibodies