Neuropeptide Y-stimulated [³⁵S]GTPγs functional binding is reduced in the hippocampus after kainate-induced seizures in mice

Abstract

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.

Neuropeptide Y is Up-regulated and Induces Antinociception in Cancer-induced Bone Pain

“…NPY receptor autoradiography was carried out as previously described (Woldbye et al, 2005, Elbrønd-Bek et al, 2014. Procedures were performed at RT if not stated otherwise.…”

Impact of type 1 diabetes mellitus and sitagliptin treatment on the neuropeptide Y system of rat retina

“…27 Here, we addressed the activity of NPY receptors using the [ 35 S]GTPγS binding assay in retinal slices. Other studies have reported alterations in the NPY system at specific time points, under different experimental condition and in other tissues, 45,46 highlighting that the NPY system is fairly dynamic and changes might only be detectable temporarily. However, it should be noted that by stimulating [ 35 S]GTPγS binding with NPY, we assessed the simultaneous activation of all NPY receptors.…”

“…Here, we used an experimental paradigm of 4 weeks of DM and/or 2 weeks of sitagliptin treatment. Other studies have reported alterations in the NPY system at specific time points, under different experimental condition and in other tissues, 45,46 highlighting that the NPY system is fairly dynamic and changes might only be detectable temporarily. Taken together, the findings from our study demonstrate that after 4 weeks of DM, NPY mRNA and protein levels decrease in diabetic retina.…”

Neuropeptide Y Negatively Influences Monocyte Recruitment to the Central Nervous System during Retrovirus Infection

“…Treatment with NPY has been shown to have therapeutic effects for both kainate-and trimethyltin-induced seizure models of temporal lobe epilepsy (43,44). The major protective effect of NPY in these models is thought to be through direct stimulation of neurons.…”