title: Inhibition of brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression reduces dopaminergic sprouting in the injured striatum.
abstract: After striatal injury, sprouting dopaminergic fibres grow towards and intimately surround wound macrophages which, together with microglia, express the dopaminergic neurotrophic factors glial cell line-derived neurotrophic factor (GDNF) and brain derived neurotrophic factor (BDNF). To evaluate the importance of these endogenously secreted neurotrophic factors in generating striatal peri-wound dopaminergic sprouting, the peri-wound expression of BDNF or GDNF was inhibited by intrastriatal infusion of antisense oligonucleotides for 2 weeks in mice. Knock-down of both BDNF and GDNF mRNA and protein levels in the wounded striatum were confirmed by in situ hybridization and enzyme-linked immunosorbent assay, respectively. Dopamine transporter immunohisto-chemistry revealed that inhibition of either BDNF or GDNF expression resulted in a marked decrease in the intensity of peri-wound sprouting. Quantification of this effect using [H3]-mazindol autoradiography confirmed that peri-wound sprouting was significantly reduced in mice receiving BDNF or GDNF antisense infusions whilst control infusions of buffered saline or sense oligonucleotides resulted in the pronounced peri-wound sprouting response normally associated with striatal injury. BDNF and GDNF thus appear to be important neurotrophic factors inducing dopaminergic sprouting after striatal injury.
authors.affiliation: Department of Medicine, University of Melbourne, Austin, Australia.
authors.forename: P E
authors.initials: PE
authors.lastname: Batchelor
authors.forename: G T
authors.initials: GT
authors.lastname: Liberatore
authors.forename: M J
authors.initials: MJ
authors.lastname: Porritt
authors.forename: G A
authors.initials: GA
authors.lastname: Donnan
authors.forename: D W
authors.initials: DW
authors.lastname: Howells
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D051100:Glial Cell Line-Derived Neurotrophic Factor; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017072:Neostriatum / Q000378:metabolism / Q000503:physiopathology* / Q000601:surgery; D009414:Nerve Growth Factors; D009416:Nerve Regeneration / Q000187:drug effects* / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects / Q000235:genetics
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C495040:Gdnf protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D004298:Dopamine