Elbrønd-Bek, Heidi2; Olling, Janne Damm3; Gøtzsche, Casper R3; Waterfield, Alison3; Wörtwein, Gitta4; Woldbye, David P D3
1 Neuropsykiatrisk laboratorium, Psykiatrisk Center København, Mental Health Services, The Capital Region of Denmark2 University of Copenhagen3 unknown4 Psykiatrisk Center København, Mental Health Services, The Capital Region of Denmark
Kainate-induced seizures constitute a model of temporal lobe epilepsy where prominent changes are observed in the hippocampal neuropeptide Y (NPY) system. However, little is known about the functional state and signal transduction of the NPY receptor population resulting from kainate exposure. Thus, in this study, we explored functional NPY receptor activity in the mouse hippocampus and neocortex after kainate-induced seizures using NPY-stimulated [(35) S]GTPγS binding. Moreover, we also studied levels of [(125) I]-peptide YY (PYY) binding and NPY, Y1, Y2, and Y5 receptor mRNA in these kainate-treated mice. Functional NPY binding was unchanged up to 12 h post-kainate, but decreased significantly in all hippocampal regions after 24 h and 1 week. Similarly, a decrease in [(125) I]-PYY binding was found in the dentate gyrus (DG) 1 week post-kainate. However, at 2 h, 6 h, and 12 h, [(125) I]-PYY binding was increased in all regions, and in the CA1 also at 24 h post-kainate. NPY mRNA levels were prominently increased in hippocampal regions, reaching maximum at 12 and 24 h. Y1 and Y5 mRNA levels were lowered in the DG at 24 and 2 h, respectively, while Y2 mRNA levels were elevated at 24 h in the DG and CA3. This study confirms rat kainate studies by showing pronounced adaptive changes in the mouse hippocampus both with regard to NPY synthesis and NPY receptor synthesis and binding, which may contribute to regulating neuronal seizure susceptibility after kainate. However, the potential seizure-suppressant effects of increased NPY gene expression at late time points post-kainate could be attenuated by the novel finding of reduced NPY-receptor G-protein activation.
Synapse (new York, N.y.), 2014, Vol 68, Issue 10, p. 427-36