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.