Restoration of splenic noradrenergic nerve fibers and immune reactivity inold F344 rats: a comparison between L-deprenyl and L-desmethyldeprenyl

L-deprenyl, a monoamine oxidase-B inhibitor, partially reversed the age-ass ociated decline in splenic sympathetic noradrenergic (NA) innervation and i mmune reactivity in old male rats. The purpose of the present study was to examine whether the effects of deprenyl on splenic sympathetic NA nerve fib ers and immune functions are mediated through a metabolite of deprenyl, L-d esmethyldeprenyl. Old male F344 rats were treated with 0, 0.25, or 1.0 mg L -(-)-deprenyl/kg BW; 0.025, 0.25, or 1.0 mg L-(-)-desmethyideprenyl/kg BW; and 1.0 mg D-(+)-desmethyldeprenyl/kg BW i.p. daily for 8 weeks. The animal s were sacrificed after a 10-day drug wash-out period and the spleens were removed for histofluorescence, immunocytochemistry, neurochemical, and immu nological analysis. The volume density of NA nerve fibers was increased in the spleens of deprenyl- and L-desmethyldeprenyl-treated old rats. Con A-in duced IFN-gamma production by spleen cells was elevated in 1.0 mg/kg depren yl- and L-desmethyldeprenyl-treated rats in comparison to saline- and D-des methyldeprenyl-treated old rats. Deprenyl and desmethyldeprenyl treatment d id not alter the percentage of CD5+ T cells, but treatment with 1.0 mg/kg d eprenyl and 0.025 mg/kg L-desmethyldeprenyl prevented the decline in the pe rcentage of sIgM(+)B cells in the spleens of old rats. These results sugges t that L-desmethyldeprenyl may be as equipotent as deprenyl in preventing a ge-associated diminution in splenic sympathetic NA innervation and immunoco mpetence. (C) 2000 International Society for Immunopharmacology. Published by Elsevier Science Ltd. All rights reserved.