phosphorus-radioisotopes and Nerve-Degeneration

Kainic acid (KA) induces status epilepticus in both adult and young rats but with different consequences on pathology and gene expression. In adults, GluR2(B) AMPA subunit expression is markedly reduced in CA3 neurons before neurodegeneration. In pups, the GluR2(B) subunit is sustained, possibly contributing to neuronal survival. Mechanisms underlying the reduced vulnerability of developing neurons to seizures was investigated by examining the effects of unilateral microinfusions of GluR2(B) antisense oligodeoxynucleotides (AS-ODNs) into the hippocampus of young rats in the presence or absence of a subconvulsive dose of KA. GluR2(B) AS-ODN infusions resulted in spontaneous seizure-like behavior, high stimulus intensity population spikes in the absence of long-term potentiation, and neurodegeneration of CA3 neurons lateral to the infusion site. Electroencephalography revealed paroxysmal activity and high-frequency high-amplitude discharges associated with vigorous and continuous scratching, wild running, or bilateral jerking movements. Pups lacking phenotypic behavior exhibited high-rhythmic oscillations and status epilepticus by the dose of KA used. Radiolabeled AS-ODNs accumulated throughout the ipsilateral dorsal hippocampus. GluR2(B) but not GluR1(A) receptor protein was markedly reduced after GluR2(B) knockdown. In contrast, GluR1(A) knockdown reduced GluR1(A) but not GluR2(B) protein without change in behavior or morphology. Therefore, unilateral downregulation of hippocampal GluR2(B) but not GluR1(A) protein reduces the seizure threshold and survival of CA3 neurons in the immature hippocampus, possibly providing a novel partial seizure model in the developing rat.

Topics: Animals; Autoradiography; Electroencephalography; Epilepsies, Partial; Functional Laterality; Hippocampus; Infusions, Parenteral; Interleukin-11 Receptor alpha Subunit; Long-Term Potentiation; Male; Nerve Degeneration; Oligodeoxyribonucleotides, Antisense; Phosphorus Radioisotopes; Rats; Rats, Sprague-Dawley; Receptors, AMPA; Receptors, Interleukin; Receptors, Interleukin-11; Seizures

Inorganic phosphate exchanges between plasma and sciatic nerve have been measured in the rabbit using a 32PO4 tracer technique. Inorganic phosphate is taken up at the rate of 0.13 microng per hour and per 100 mg fresh weight. Incorporation of plasma radiophosphate is markedly increased into the inorganic and organic acid soluble phosphate fractions of the distal part of the sectioned sciatic nerve. This increase is already signficant within one hour after surgical division, spreading at least 3 cm distally within 6 hours. This high level of incorporation persists until the 29th day of degeneration. These results favour the hypothesis that the axonal continuity maintains the metabolic activity of the Schwann cells at an inframaximal level. We confirm the rapid decrease in total phospholipid concentration in the nerve undergoing Wallerian degeneration as well as the marked increase in their specific activity. We show however that this increase in specific activity is due partly to the increased specific activities of the precursors (organic acid soluble phosphates), partly to the disappearance of a metabolically insert pool (myelin phospholipids). The Schwann cells of the nerve undergoing Wallerian degeneration do not have a more active phospholipid metabolism than their normal counterparts.

Topics: Animals; Kinetics; Male; Nerve Degeneration; Organophosphorus Compounds; Phosphates; Phospholipids; Phosphorus Radioisotopes; Rabbits; Sciatic Nerve; Time Factors; Wallerian Degeneration

Plasma inorganic phosphate incorporation into inorganic and organic acid soluble phosphate fractions of the rat sciatic nerve shows, for one week after the operation, parallel increases in both crushed and sectioned nerves. After two weeks the incorporation in the distal part of the crushed nerve shows a progressive return to normal values remaining however significantly increased until the 90th day. These experiments confirm the possibility of an axonal inhibitory control on the Schwann cell metabolism.

Topics: Animals; Axons; Denervation; Female; Muscles; Nerve Crush; Nerve Degeneration; Nerve Regeneration; Organophosphorus Compounds; Phosphates; Phosphorus Radioisotopes; Rats; Schwann Cells; Sciatic Nerve; Time Factors; Wallerian Degeneration

Topics: Animals; Injections, Intraperitoneal; Kinetics; Male; Nerve Degeneration; Organophosphorus Compounds; Phosphates; Phosphorus Radioisotopes; Rats; Sciatic Nerve; Wallerian Degeneration

Topics: Acids; Animals; Axons; Denervation; Male; Nerve Degeneration; Organophosphorus Compounds; Phosphates; Phosphorus Radioisotopes; Rats; Schwann Cells; Sciatic Nerve; Solubility; Time Factors; Wallerian Degeneration; Water

Topics: Nerve Degeneration; Nervous System; Phosphorus; Phosphorus Radioisotopes