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 motoneurons with an efficacy comparable to that of the neurotrophic factors 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 may be mediated through reactive 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 cortex. After mechanical wounding, PB astrocytes preferentially migrate into the wound zone while flat astrocytes maintain their position at the wound edge. CNTF mRNA was localized to PB astrocytes, but not flat astrocytes, as determined by in situ hybridization using biotin-labelled 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)-10(-11) M) 48 hr after injury. (-)-Deprenyl also increased the total process length of PB astrocytes after wounding 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 upregulate CNTF gene expression in astroglial cell culture as well as influence glial cell process length.(ABSTRACT TRUNCATED AT 250 WORDS)
Seniuk
N A
NA
S. Lunenfeld Research Institute, Mt. Sinai Hospital, Toronto, Canada.
Henderson
J T
JT
Tatton
W G
WG
Roder
J C
JC
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor; D020934:Ciliary Neurotrophic Factor; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis / Q000276:immunology; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D009414:Nerve Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D015347:RNA Probes; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012642:Selegiline / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects; D014746:Vimentin / Q000096:biosynthesis / Q000276:immunology
D019208:Brain-Derived Neurotrophic Factor; D020934:Ciliary Neurotrophic Factor; D005904:Glial Fibrillary Acidic Protein; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D015347:RNA Probes; D012333:RNA, Messenger; D014746:Vimentin; D012642:Selegiline