Spinal cord interneuron degenerative atrophy caused by peripheral nerve lesions is prevented by serotonin depletion

Abstract

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)

Denervation and hyperinnervation in the nervous system of diabetic animals. I. The autonomic neuronal dystrophy of the gut

“…The homogenate was split into two aliquots, one for 5-hydroxyindoles (5-HT and 5-HIAA) and the other for catecholamines (NA and DA) quantification. The aliquot for 5-HT and 5-HIAA assay was centrifuged at 40,OOOg for 15 min and the resulting supernatant diirectly injected into the HPLC apparatus (Di Giulio et al, 1987). Catecholamine assay required an intermediate purification step by adsorption into allumina.…”

Perinatal supplementation of low doses of ethanol enhances 5-HT restoration in the central nervous system

“…Animals were kept under standard conditioned and killed at the appropriate time. Brain and spinal cord were quickly dissected out, frozen in liquid nitrogen and kept at -80°C until assay (Di Giulio et al, 1987, 1989aGorio et al, 1993Gorio et al, , 1996. An approximate equal number of female and male animals were studied in each group.…”

Glycosaminoglycans in nerve injury: II. Effects on transganglionic degeneration and on the expression of neurotrophic factors

“…previously published procedures (Di Giulio et al, 1987, 1989. Briefly, 21 days after sciatic nerve resection animals were anesthetized with 30 mg/kg pentobarbital i.p.…”

“…Also substantia gelatinosa interneurons undergo atrophy following sciatic nerve lesion, and it has been shown that in the dorsal horn there is loss of metenkephalin (Met-Enk) and the relative neurons undergo atrophy (Di Giulio et al, 1985, 1989. The MetEnk changes are regulated by the descending serotoninergic pathways and activated b y the sciatic nerve lesion (Di Giulio et al, 1987). In addlition there is a 40% loss of opiate receptors (Ninkovic et al, 1981).…”