title: Galanin antisense oligonucleotides reduce galanin levels in dorsal root ganglia and induce autotomy in rats after axotomy.
abstract: Antisense (AS) oligonucleotides (ONs) to galanin (GAL) were applied to the proximal end of a transected sciatic nerve, allowing their cellular uptake and transport into injured axons. GAL expression in dorsal root ganglia and self-mutilation behavior (autotomy) were then studied. AS-ONs with phosphorothioate or allyl modifications significantly suppressed the axotomy-induced increase in GAL levels, as demonstrated by immunohistochemistry and exaggerated autotomy behavior, whereas no significant effect on GAL mRNA levels could be demonstrated with in situ hybridization. Allyl-ONs were more effective than phosphorothioate-ONs. An AS-ON with three base mismatches did not induce any of the above effects. These results support the view that the inhibition of axotomy-induced GAL up-regulation is related to autotomy.
authors.affiliation: Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
authors.forename: R R
authors.initials: RR
authors.lastname: Ji
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
authors.forename: K
authors.initials: K
authors.lastname: Bedecs
authors.forename: J
authors.initials: J
authors.lastname: Arvidsson
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: X J
authors.initials: XJ
authors.lastname: Xu
authors.forename: Z
authors.initials: Z
authors.lastname: Wiesenfeld-Hallin
authors.forename: T
authors.initials: T
authors.lastname: Bartfai
authors.forename: T
authors.initials: T
authors.lastname: Hökfelt
mesh_terms: D000818:Animals; D001483:Base Sequence; D005455:Fluorescent Antibody Technique; D019004:Galanin; D005727:Ganglia, Spinal / Q000378:metabolism*; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D009473:Neuronal Plasticity; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000494:pharmacology*; D010455:Peptides / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012652:Self Mutilation / Q000503:physiopathology*
chemical_list: D016376:Oligonucleotides, Antisense; D010455:Peptides; D012333:RNA, Messenger; D019004:Galanin