INCREASED CNTF GENE-EXPRESSION IN PROCESS-BEARING ASTROCYTES FOLLOWING INJURY IS AUGMENTED BY R(-)-DEPRENYL

R(-)-deprenyl has been shown to rescue axotomized immature facial moto neurons with an efficacy comparable to that of the neurotrophic factor s CNTF and BDNF (Salo and Tatton, J Neurosci Res 31:394-400, 1992; Ans ari et al., J Neurosci 13:4042-4053, 1993). Recent work has suggested that some of the actions of (-)-deprenyl may be mediated through react ive astrocytes (Biagini et al., NeuroReport 4:955-958, 1993). To test this proposal we have developed an in vitro model of reactive gliosis consisting of a mixed astrocyte population of flat and process-bearing (PB) astroglia taken from postnatal day (PD) 2 or PD5 rat cerebral co rtex. After mechanical wounding, PB astrocytes preferentially migrate into the wound zone while flat astrocytes maintain their position at t he wound edge. CNTF mRNA was localized to PB astrocytes, but not flat astrocytes, as determined by in situ hybridization using biotin-labell ed riboprobes. Following ''wounding,'' there was an increase in CNTF m RNA in PB astrocytes only, which could be further enhanced by a single pulse of (-)-deprenyl (10(-8)-10(-11) M) 48 hr after injury. (-)-Depr enyl also increased the total process length of PB astrocytes after wo unding by an average of 50%. The stereoisomer (+)-deprenyl (10(-9) M) had no effect on either astrocyte process length or CNTF mRNA content. This is the first report to our knowledge of an agent which can upreg ulate CNTF gene expression in astroglial cell culture as well as influ ence glial cell process length. We propose that some of the trophic-li ke actions of (-)-deprenyl may be mediated through a specific subpopul ation of astroglia. (C) 1994 Wiley-Liss, Inc.