title: Accumulated increase in neuropeptide Y and somatostatin gene expression of the rat in response to repeated electroconvulsive stimulation.
abstract: The mechanisms by which electroconvulsive therapy (ECT) causes its antidepressive effect are unknown. Because ECT requires repeated induction of electroconvulsive seizures, adaptive changes in the brain and regulation of gene expression, are likely to be the fundamental basis on which ECT acts. Neuropeptide Y (NPY) gene expression is increased after multiple electroconvulsive stimulations (ECS) and since it also has anticonvulsant and antidepressant properties, it has led to the hypothesis that the beneficial effect of ECT is mediated via its activation of NPY-dependent neurotransmission. We have therefore examined in detail the temporal profile of NPY gene expression, using in situ hybridisation histochemistry in the rat dentate gyrus and piriform cortex - two brain areas centrally involved in seizure regulation. NPY mRNA in both regions was found to increase gradually with the number of ECS, reaching a maximum (550-700%) after approximately 14 ECS where no further increase was achieved by additional ECS. A number of 14 ECS was also shown to exert anticonvulsant activity against kainic acid seizures. In the dentate gyrus, repeated ECS also caused a gradual, but smaller, increase in the expression of somatostatin (SS) - a neuropeptide that is co-localised with NPY and also has anticonvulsant effects. These results shows that NPYergic and, to a lesser extent, SSergic neurotransmission is activated by ECS and support the hypothesis that these neuropeptides could play a central role in the anticonvulsant and antidepressant effect of ECT.
authors.affiliation: Department of Molecular Anatomy and Physiology, NeuroSearch A/S, Pederstrupvej 93, 2750 Ballerup, Denmark. JDM@Neurosearch.dk
authors.forename: Jens D
authors.initials: JD
authors.lastname: Mikkelsen
authors.forename: David P D
authors.initials: DP
authors.lastname: Woldbye
mesh_terms: D000818:Animals; D018891:Dentate Gyrus / Q000378:metabolism; D004565:Electroconvulsive Therapy / Q000379:methods*; D015870:Gene Expression / Q000235:genetics*; D006624:Hippocampus / Q000378:metabolism; D017403:In Situ Hybridization; D008297:Male; D009478:Neuropeptide Y / Q000235:genetics* / Q000378:metabolism*; D010507:Periodicity; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000235:genetics; D013004:Somatostatin / Q000235:genetics* / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology; D015854:Up-Regulation
chemical_list: D009478:Neuropeptide Y; D013004:Somatostatin