title: Suppression of spreading depression-like events in locusts by inhibition of the NO/cGMP/PKG pathway.
abstract: Despite considerable research attention focused on mechanisms underlying neural spreading depression (SD), because of its association with important human CNS pathologies, such as stroke and migraine, little attention has been given to explaining its occurrence and regulation in invertebrates. In the locust metathoracic ganglion (MTG), an SD-like event occurs during heat and anoxia stress, which results in cessation of neuronal output for the duration of the applied stress. SD-like events were characterized by an abrupt rise in extracellular potassium ion concentration ([K(+)](o)) from a baseline concentration of approximately 8 to >30 mm, which returned to near baseline concentrations after removal of the applied stress. After return to baseline [K(+)](o), neuronal output (ventilatory motor pattern activity) from the MTG recovered. Unlike mammalian neurons, which depolarize almost completely during SD, locust neurons only partially depolarized. SD-like events in the locust CNS were suppressed by pharmacological inhibition of the nitric oxide/cyclic guanosine monophosphate/protein kinase G (NO/cGMP/PKG) pathway and were exacerbated by its activation. Also, environmental stressors such as heat and anoxia increased production of nitric oxide in the locust CNS. Finally, for the intact animal, manipulation of the pathway affected the speed of recovery from suffocation by immersion under water. We propose that SD-like events in locusts provide an adaptive mechanism for surviving extreme environmental conditions. The highly conserved nature of the NO/cGMP/PKG signaling pathway suggests that it may be involved in modulating SD in other organisms, including mammals.
authors: Department of Biology, Queen's University, Kingston, Ontario K7L 3N6, Canada.
authors: Gary A B
authors: GA
authors: Armstrong
authors: Corinne I
authors: CI
authors: Rodgers
authors: Tomas G A
authors: TG
authors: Money
authors: R Meldrum
authors: RM
authors: Robertson
mesh_terms: D000818:Animals; D013181:Cortical Spreading Depression / Q000187:drug effects / Q000502:physiology*; D006152:Cyclic GMP / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006110:Grasshoppers / Q000378:metabolism; D006358:Hot Temperature / Q000009:adverse effects; D000860:Hypoxia / Q000150:complications; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013312:Stress, Physiological
chemical_list: D020030:Nitric Oxide Donors; D010726:Phosphodiesterase Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP; D011188:Potassium