N.A. Seniuk*, J.T. Henderson*, W.G. Tatton#,and John Roder*
* Samuel Lunenfeld Research Institute, Mount SinaiHospital,
Program and Development and FetalHealth, 600 University Ave., Toronto, Ontario M5G-1X5
# Neurodegenerative Diseases and Department ofPsychiatry,
University of Toronto, Toronto,Canada
Journal of Neuroscience Research,37(2), pp. 278-286, 1994
Abstract
R(-)-Deprenyl has been shown torescue axotomized immature facial motor neurons with an efficacy comparableto that of the neurotrophic factor CNTF and BDNF (Salo and Tatton, J. Neurosci.Res. 31:394-400, 1992; Ansari et al. J. Neurosci. 13:4042-4053, 1993).recent work has suggested that some of the actions of (-)-deprenyl maybe mediated through reactive astrocytes (Biagini et al., NeuroReport 4:955-958,1993) To test this proposal we have developed an in vitro model of reactivegliosis consisting of a mixed astrocyte population of flat and process-bearing(PB) astroglia taken from postnatal day (PD) 2 or PD5 rat cerebral cortex.After mechanical wounding, PB a astrocytes preferentially migrate intothe wound zone while flat astrocytes maintain their position as the wound edge. CNTF mRNA was localized to PB astrocytes, but not flat astrocytes,as determined by in situ hybridization using biotin-labeled riboprobes.Following wounding, there was an increase in CNTF mRNA in PB astrocytes only, which could be further enhanced by a single pulse of (-)-deprenyl(10-8 to 10-11 M) 48 hours after injury. (-)-deprenyl also increased thetotal process length of PB astrocytes after wounding by an average of 50%.The stereo-isomer (+)-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 up-regulate CNTF gene expression in astroglial cell culture as well as influence glial cell process length. We propose that some of the trophic-like actions of (-)-Deprenyl may be mediated through a specific sub-population of astroglia.
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