Neuronal Conduction of Excitation without Action Potentials Based on Ceramide Production

International audienceBACKGROUND: Action potentials are the classic mechanism by which neurons convey a state of excitation throughout their length, leading, after synaptic transmission, to the activation of other neurons and consequently to network functioning. Using an in vitro integrated model, we found previously that peripheral networks in the autonomic nervous system can organise an unconventional regulatory reflex of the digestive tract motility without action potentials. METHODOLOGY/PRINCIPAL FINDINGS: In this report, we used combined neuropharmacological and biochemical approaches to elucidate some steps of the mechanism that conveys excitation along the nerves fibres without action potentials. This mechanism requires the production of ceramide in membrane lipid rafts, which triggers in the cytoplasm an increase in intracellular calcium concentration, followed by activation of a neuronal nitric oxide synthase leading to local production of nitric oxide, and then to guanosine cyclic monophosphate. This sequence of second messengers is activated in cascade from rafts to rafts to ensure conduction of the excitation along the nerve fibres. CONCLUSIONS/SIGNIFICANCE: Our results indicate that second messengers are involved in neuronal conduction of excitation without action potentials. This mechanism represents the first evidence-to our knowledge-that excitation is carried along nerves independently of electrical signals. This unexpected ceramide-based conduction of excitation without action potentials along the autonomic nerve fibres opens up new prospects in our understanding of neuronal functioning

Medium-size-vessel vasculitis

Medium-size-artery vasculitides do occur in childhood and manifest, in the main, as polyarteritis nodosa (PAN), cutaneous PAN and Kawasaki disease. Of these, PAN is the most serious, with high morbidity and not inconsequential mortality rates. New classification criteria for PAN have been validated that will have value in epidemiological studies and clinical trials. Renal involvement is common and recent therapeutic advances may result in improved treatment options. Cutaneous PAN is a milder disease characterised by periodic exacerbations and often associated with streptococcal infection. There is controversy as to whether this is a separate entity or part of the systemic PAN spectrum. Kawasaki disease is an acute self-limiting systemic vasculitis, the second commonest vasculitis in childhood and the commonest cause of childhood-acquired heart disease. Renal manifestations occur and include tubulointerstitial nephritis and renal failure. An infectious trigger and a genetic predisposition seem likely. Intravenous immunoglobulin (IV-Ig) and aspirin are effective therapeutically, but in resistant cases, either steroid or infliximab have a role. Greater understanding of the pathogenetic mechanisms involved in these three types of vasculitis and better long-term follow-up data will lead to improved therapy and prediction of prognosis