GALANIN ANTISENSE OLIGONUCLEOTIDES REDUCE GALANIN LEVELS IN DORSAL-ROOT GANGLIA AND INDUCE AUTOTOMY IN RATS AFTER AXOTOMY

Antisense (AS) oligonucleotides (ONs) to galanin (GAL) were applied to the proximal end of a transected sciatic nerve, allowing their cellul ar uptake and transport into injured axons. GAL expression in dorsal r oot ganglia and self-mutilation behavior (autotomy) were then studied. AS-ONs with phosphorothioate or allyl modifications significantly sup pressed the axotomy-induced increase in GAL levels, as demonstrated by immunohistochemistry and exaggerated autotomy behavior, whereas no si gnificant effect on GAL mRNA levels could be demonstrated with in situ hybridization. Allyl-ONs were more effective than phosphorothioate-ON s. An AS-ON with three base mismatches did not induce any of the above effects. These results support the view that the inhibition of arotom y-induced GAL up-regulation is related to autotomy.