Spinal cord interneuron degenerative atrophy caused by peripheral nerve lesions is prevented by serotonin depletion.
Peripheral nerve section causes a degenerative atrophy of substance P sensory input and of met-enkephalin interneurons in the dorsal horn of the spinal cord. Radioimmunoassay of both peptides indicates that the decrease in peptide levels ranges from 30 to 50%, that it occurs several days after lesioning, and that it is simultaneous for the two peptides. Quantitative immunocytochemistry performed by computer-assisted analysis of met-enkephalin-positive boutons shows that following sciatic nerve lesions there is a decreased density of immunoreactive boutons per unit area in the substantia gelatinosa of the dorsal horn in the lumbar cord ipsilateral to the lesion. Within 24 h of nerve injury there is a significant and transient enhancement of serotonin turnover, as indicated by the increased levels of 5-hydroxyindolacetic acid in the lumbar cord, without any change in serotonin concentrations. The restoration of normal serotonin metabolism at d 10 postlesioning coincides with the peptidergic loss. However, if, prior to nerve resection, serotonin stores are depleted by p-chlorophenylalanine treatment, the damage to met-enkephalin interneurons is fully prevented, while substance P loss does still occur. These results suggest that signals caused by the section of a peripheral nerve are directly responsible for substance P loss in the spinal cord and are, presumably, rapidly transported into the CNS, causing an activation of the serotoninergic raphe neurons projecting to spinal cord. The activation of this system is likely responsible for the degenerative atrophy of the met-enkephalin interneurons.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001284:Atrophy; D004744:Enkephalin, Methionine / Q000378:metabolism / Q000502:physiology; D007395:Interneurons / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009410:Nerve Degeneration / Q000187:drug effects*; D009434:Neural Pathways / Q000378:metabolism / Q000473:pathology; D010525:Peripheral Nerves / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000378:metabolism / Q000502:physiology; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology*; D013373:Substance P / Q000378:metabolism / Q000502:physiology
D012701:Serotonin; D013373:Substance P; D004744:Enkephalin, Methionine