Altered Expression of NPY-Y1 and -Y2 Receptors in the Hippocampus of Patients with Mesial Temporal Lobe Epilepsy
Abstract number :
1.083
Submission category :
Year :
2000
Submission ID :
2385
Source :
www.aesnet.org
Presentation date :
12/2/2000 12:00:00 AM
Published date :
Dec 1, 2000, 06:00 AM
Authors :
Guenther Sperk, Susanne Kandlhofer, Sabine Furtinger, Thomas Czech, Christoph Baumgartner, Dept of Pharmacology, A-6020-Innsbruck, Austria; Dept of Neurosurgery, Wien, Austria; Dept of Pharmacology, Innsbruck, Austria; Dept of Neurology, Wien, Austria.
Rationale Increases in the expression of neuropeptide Y (NPY) and of NPY-Y2 receptors in granule cells/mossy fibers, and down-regulation of NPY-Y1 receptors in the molecular layer of the dentate gyrus have been found after kainic acid-induced seizures in the rat. We now investigated changes in NPY-immunoreactivity and Y1 and Y2 receptor binding in the hippocampus of patients with mesial temporal lobe epilepsy and post-mortem controls. Methods Surgically removed tissue was collected from 12 patients with intractable mesial temporal lobe epilepsy and post-mortem from 9 non-neurologically deceased patients. The tissue was either snap-frozen in isopentane at -70 C for in situ-hybridization and receptor autoradiography or fixed in 4 % paraformaldehyde for immunocytochemistry.For receptor autoradiography125I-[Pro]PYY and125I-PYY(3-36) were used as ligands for Y1 and Y2 receptors, respectively. NPY-immunocytochemistry was done by indirect labeling with a peroxidase-antiperoxidase system. In situ-hybridization for NPY mRNA was performed using 35S-labeled oligonucleotide probes. Results In accordance with DeLanerolle et al., we observed marked increases in NPY-positive fiber staining in the dentate gyrus. Expression of NPYmRNA appeared to be markedly enhanced in local neurons of the subiculum and dentate hilus. In the hippocampus of post mortem controls, Y1 receptor binding was mainly observed in the dentate molecular layer. Y2 receptor binding was high in the dentate hilus and the strata radiatum and oriens of CA1 to CA3. In the hippocampi of epilepsy patients, Y1 receptor binding was significantly reduced. In contrast, a strong increase in Y2 receptor binding was observed in the dentate hilus. Conclusions It has been previously suggested that NPY may exert proconvulsive effects through Y1 receptors and an anticonvulsive action, mediated by presynaptic inhibition of glutamate release, by Y2 receptors. The neurochemical changes therefore may represent protective mechanisms in epilepsy. This work was supported by the Austrian Scientific Research Funds and the Ministery of Science.