Insulin-like growth factor-I counteracts bFGF-induced survival of nitric oxide synthase (NOS)-positive spinal cord neurons after target-lesion in vivo.
We have used nitric oxide synthase (NOS) histochemistry as a perikaryal viability marker to trace the retrograde reaction of spinal cord intermediolateral (IML) sympathoadrenal projection (SAP)-neurons to target-removal, i.e., selective adrenomedullectomy and local administration of either insulin-like growth factor-I (IGF-I), basic fibroblast growth factor (bFGF) or a combination of both. Counting of NOS-positive preganglionic spinal cord neurons 4 weeks post surgery indicated that more than 80% of stained neurons were lost from the IML-cell column. This percentage loss corresponds to the numerical loss of NOS-stained SAP-neurons labeled retrogradely with Fast-blue prior to adrenomedullectomy. Basic FGF-supplementation at the site of lesion resulted in maintenance of the majority of NOS-positive IML-neurons, a finding confirmed by the survival rate of Fast-blue prelabeled SAP-neurons. Thus, besides maintenance of the structural integrity of SAP-neurons, bFGF prevents loss of intracellular NOS-activity which may reflect unaltered cell metabolism (and function) of these neurons following target-removal in vivo. By contrast, IGF-I failed to alter the rate of disappearance of NOS-staining and labeling index of neurons within the IML-cell column postlesion, suggesting that IGF-I is not neurotrophic for SAP-neurons by itself. Combined treatment with both factors resulted in a more widespread loss of NOS-stained and Fast-blue-prelabeled SAP-neurons than registered after bFGF-only treatment. No co-trophic effect of bFGF and IGF-I was evident; rather, the pronounced bFGF-induced rescuing effect was significantly suppressed by exogenous IGF-I in vivo, supporting the idea that this or another molecule induced by the treatment enhances rather than prevents retrograde degeneration and neuronal death within the adult lesioned IML-adrenal pathway.
Blottner
D
D
Department of Anatomy, Free University of Berlin, Germany.
Baumgarten
H G
HG
D000313:Adrenal Medulla / Q000502:physiology; D000315:Adrenalectomy; D000594:Amino Acid Oxidoreductases / Q000378:metabolism*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006651:Histocytochemistry; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D009252:NADPH Dehydrogenase / Q000032:analysis; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D019001:Nitric Oxide Synthase; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects
D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D009252:NADPH Dehydrogenase