DEPRENYL INDUCES GFAP IMMUNOREACTIVITY IN THE INTACT AND INJURED DOPAMINERGIC NIGROSTRIATAL SYSTEM BUT FAILS TO COUNTERACT AXOTOMY-INDUCED DEGENERATIVE CHANGES

There is increasing evidence of a trophic-like mechanism for some effe cts ascribed to deprenyl therapy in the central nervous system. For th at, we studied the effect of chronic treatment with deprenyl in an ani mal model of Parkinson's disease induced by unilateral knife transecti on of the medial forebrain bundle (MFB) in adult rats. The experimenta l conditions included a 3-week pretreatment with deprenyl before stere otaxic transection of the MFB. Following surgery, deprenyl treatment w as maintained for 3 weeks. Neurochemical and immunohistochemical proce dures were used to study the dopaminergic system and reactive astrocyt es in the nigrostriatal system. Deprenyl treatment failed to counterac t the axotomy-induced degenerative changes of the nigrostriatal dopami nergic system. However, it was effective in increasing the density of reactive astrocytes in terms of glial fibrillary acidic protein (GFAP) immunoreactivity in the intact contralateral substantia nigra and als o in further enhancing the axotomy-induced increase of GFAP immunolabe led astrocytes in the lesioned substantia nigra. This deprenyl-induced effect on GFAP immunoreactivity was confined to substantia nigra with out effect in striatum. In addition, we found a medial to lateral grad ient decrease in the distribution pattern of GFAP immunolabeled astroc ytes. Axotomy increased the number of reactive astrocytes in either st riatal area examined, but yet the preferential distribution pattern of reactive astrocytes in striatum was still evident. (C) 1997 Wiley-Lis s, Inc.