Restoration of splenic noradrenergic nerve fibers and immune reactivity in old F344 rats: a comparison between L-deprenyl and L-desmethyldeprenyl.
L-deprenyl, a monoamine oxidase-B inhibitor, partially reversed the age-associated decline in splenic sympathetic noradrenergic (NA) innervation and immune reactivity in old male rats. The purpose of the present study was to examine whether the effects of deprenyl on splenic sympathetic NA nerve fibers and immune functions are mediated through a metabolite of deprenyl, L-desmethyldeprenyl. 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-(-)-desmethyldeprenyl/kg BW; and 1.0 mg D-(+)-desmethyldeprenyl/kg BW i.p. daily for 8 weeks. The animals were sacrificed after a 10-day drug wash-out period and the spleens were removed for histofluorescence, immunocytochemistry, neurochemical, and immunological analysis. The volume density of NA nerve fibers was increased in the spleens of deprenyl- and L-desmethyldeprenyl-treated old rats. Con A-induced IFN-gamma production by spleen cells was elevated in 1.0 mg/kg deprenyl- and L-desmethyldeprenyl-treated rats in comparison to saline- and D-desmethyldeprenyl-treated old rats. Deprenyl and desmethyldeprenyl treatment did not alter the percentage of CD5+ T cells, but treatment with 1.0 mg/kg deprenyl and 0.025 mg/kg L-desmethyldeprenyl prevented the decline in the percentage of sIgM(+)B cells in the spleens of old rats. These results suggest that L-desmethyldeprenyl may be as equipotent as deprenyl in preventing age-associated diminution in splenic sympathetic NA innervation and immunocompetence.
ThyagaRajan
S
S
Center for Neuroimmunology, Loma Linda University School of Medicine, 11021 Campus Street, Loma Linda, USA. sthyagarajan@som.llu.edu
Madden
K S
KS
Stevens
S Y
SY
Felten
D L
DL
D000320:Adrenergic Fibers / Q000187:drug effects / Q000276:immunology*; D000375:Aging / Q000187:drug effects / Q000276:immunology*; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects / Q000276:immunology*; D009638:Norepinephrine / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D012642:Selegiline / Q000494:pharmacology*; D013154:Spleen / Q000187:drug effects / Q000276:immunology* / Q000294:innervation*
D000662:Amphetamines; D012642:Selegiline; C017861:desmethylselegiline; D009638:Norepinephrine