PSA-NCAM distinguishes reactive astrocytes in 6-OHDA-lesioned substantia nigra from those in the striatal terminal...

6-hydroxydopamine (6-OHDA) lesion of the substantia nigra (SN) causes the appearance of reactive astrocytes not only in the SN but also in the striatal terminal fields, as measured by increased size of the cells and their processes, as well as enhanced expression of glial fibrillary acidic protein (GFAP) and an epitope recognized by monoclonal antibody 19D1. We now demonstrate that polysialylated neural cell adhesion molecule (PSA-NCAM) is induced on reactive astrocytes, as well as on large neurons, on the ipsilateral side of the 6-OHDA-lesioned SN. Colocalization of GFAP and PSA-NCAM was confirmed for reactive astrocytes using a confocal laser scanning microscope. Negligible amounts of PSA-NCAM reactivity were detected contralaterally, although colocalization was noted on astrocytes with sparse, significantly thinner processes. In contrast to the increase of GFAP in the lesioned striatum, few striatal astrocytes expressed PSA-NCAM. In agreement with these results, PSA-NCAM was detected on cultured reactive astrocytes from SN but not reactive striatal astrocytes. Double immunohistochemistry for proliferating cell nuclear antigen (PCNA), a marker of dividing cells, and GFAP demonstrated that reactive astrocytes in lesioned SN were PCNA-positive whereas those in striatum were not. Although NG2 chondroitin sulfate proteoglycan expression also increased in the lesioned SN, NG2 was not colocalized with PSA-NCAM, was not expressed on astrocytes, and labeled only oligodendrocyte precursor cells. Our results suggest that PSA-NCAM can act as a marker for reactive astrocytes only at the site of the lesion and not in the terminal fields, probably because it is reexpressed only when astrocytes divide.