ALTERED PATTERNS OF CA2+ CALMODULIN-DEPENDENT PROTEIN-KINASE-II AND CALCINEURIN IMMUNOREACTIVITY IN THE HIPPOCAMPUS OF PATIENTS WITH TEMPORAL-LOBE EPILEPSY/

Ca2+/calmodulin-dependent protein kinase II (CaMKII) and calcineurin r epresent neuronal Ca2+-dependent enzymes which dynamically modify seve ral common substrates in the mammalian brain via phosphorylation/depho sphorylation cycles. Studies in animal models indicate that altered ex pression and activity of these enzymes may be involved in epilepsy. We have analyzed their immunohistochemical distribution in hippocampi of 28 temporal lobe epilepsy (TLE) patients and 13 controls. TLE specime ns were classified as Ammon's horn sclerosis (AHS) or focal lesions wi thout alteration of hippocampal cytoarchitecture. Compared to control and lesion-associated TLE specimens, striking changes in the distribut ion pattern of both enzymes were found in the dentate gyrus (DG) of AH S specimens: Whereas CaMKII labeling was significantly increased in th e granule cell somata and their proximal dendrites, calcineurin immuno reactivity was significantly reduced in the granule cell somata. Furth ermore, calcineurin staining in controls showed high levels in the inn er molecular layer with a sharp demarcation towards the outer molecula r layer. In AHS, calcineurin staining was reduced in the inner molecul ar layer, with partial loss of this demarcation. These findings raise the possibility, that an up-regulation of CaMKII with a concomitant do wn-regulation of calcineurin in the DG of AHS specimens may cause a pa thogenetically relevant imbalance of neuronal Ca2+/calmodulin-dependen t phosphorylation/dephosphorylation systems.