Plasticity of Y1 and Y2 receptors and neuropeptide Y fibers in patients with temporal lobe epilepsy

Marked expression of neuropeptide Y (NPY) and its Y2 receptors in hippocamp al mossy fibers has been reported in animal models of epilepsy. Because NPY can suppress glutamate release by activating presynaptic Y2 receptors, the se changes have been proposed as an endogenous protective mechanism. Theref ore, we investigated whether similar changes in the NPY system may also tak e place in human epilepsy. We investigated Y1 and Y2 receptor binding and N PY immunoreactivity in hippocampal specimens that were obtained at surgery from patients with temporal lobe epilepsy and in autopsy controls. Signific ant increases in Y2 receptor binding (by 43-48%) were observed in the denta te hilus, sectors CA1 to CA3, and subiculum of specimens with, but not in t hose without, hippocampal sclerosis. On the other hand, Y1 receptor binding was significantly reduced (by 62%) in the dentate molecular layer of scler otic specimens. In the same patients, the total lengths of NPY immunoreacti ve (NPY-IR) fibers was markedly increased (by 115-958%) in the dentate mole cular layer and hilus, in the stratum lucidum of CA3, and throughout sector s CA1 to CA3 and the subiculum, as compared with autopsies. In nonsclerotic specimens, increases in lengths of NPY-IR fibers were more moderate and st atistically not significant. NPY mRNA was increased threefold in hilar inte rneurons of sclerotic and nonsclerotic specimens. It is suggested that abun dant sprouting of NPY fibers, concomitant upregulation of Y2 receptors, and downregulation of Y1 receptors in the hippocampus of patients with Ammon's horn sclerosis may be endogenous anticonvulsant mechanisms.