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

6-hydroxydopamine (6-OHDA) lesion of the substantia nigra (SN) causes the a ppearance of reactive astrocytes not only in the SN but also in the striata l terminal fields, as measured by increased size of the cells and their pro cesses, as well as enhanced expression of glial fibrillary acidic protein ( GFAP) and an epitope recognized by monoclonal antibody 19D1. We now demonst rate that polysialylated neural cell adhesion molecule (PSA-NCAM) is induce d on reactive astrocytes, as well as on large neurons, on the ipsilateral s ide of the 6-OHDA-lesioned SN. Colocalization of GFAP and PSA-NCAM was conf irmed for reactive astrocytes using a confocal laser Scanning microscope. N egligible amounts of PSA-NCAM reactivity were detected contralaterally, alt hough colocalization was noted on astrocytes with sparse, significantly thi nner processes, In contrast to the increase of GFAP in the lesioned striatu m, few striatal astrocytes expressed PSA-NCAM. In agreement with these resu lts, 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 demonstr ated that reactive astrocytes in lesioned SN were PCNA-positive whereas tho se in striatum were not. Although NG2 chondroitin sulfate proteoglycan expr ession also increased in the lesioned SN, NG2 was not colocalized with PSA- NCAM, was not expressed on astrocytes, and labeled only oligodendrocyte pre cursor cells. Our results suggest that PSA-NCAM can act as a marker for rea ctive astrocytes only at the site of the lesion and not in the terminal fie lds, probably because it is reexpressed only when astrocytes divide. Publis hed 2000 Wiley-Liss, Inc.dagger