Doublecortin immunoreactivity in human hippocampal sclerosis.

D`ALESSIO L, KONOPKA H, KOCHEN S, CONSALVO D, KAUFFMAN M, LÓPEZ EM, LÓPEZ-COSTA JJ.

Seattle

Congreso; Congreso Americano de Epilepsia; 2008

Sociedad Americana de Epilepsia

Introduction Doublecortin (DCX) is a microtubule-associated phosphoprotein involved in neuronal development. In adult neurogenesis newly generated cells express DCX, which has been associated with neurite elongation and synaptogenesis. DCX has been used as a marker of newly born neurons in the adult dentate gyrus (DG), although certain granule cells with differentiated phenotype, some neurons in hippotalamus and in cerebral cortex express DCX. In epilepsy, the role of neurogenesis is controversial and only a few reports determined DCX in epileptic tissue.   Objectives The aim of this study was to determine DCX immunoreactivity in human hippocampal sclerosis from patients who underwent epilepsy surgery for intractable epilepsy. Methods Hippocampal sections of 6 patients with hippocampal sclerosis and refractory TLE (temporal lobe epilepsy), who underwent therapeutic surgery, were processed using Immunofluorescence and Immunoperoxidase for DCX. Archival material from normal post-mortem hippocampus were simultaneously processed. Staining intensity of neurons expressing DCX was determined by computarized image analysis. Results In both, control and epileptic hippocampus, DCX positive neurons were found in DG and CA1 of hippocampus. Lower staining intensity was observed in DG of epileptic hippocampus compared with normal hippocampus (transmittance 72, 8 ±4 / 66, 7 ±1; p<0.05). Heavy DCX expressing neurons were observed in CA1 of both control and epileptic hippocampus, but sections of epileptic patients showed DCX immunoreactive neurons with longer coiled apical dendrites and many reactive fibbers crossing along CA1. These observations were not present in normal hippocampus where DCX was only expressed in neuronal somas.  Conclusions Lower DCX expression was observed in DG hippocampal sclerosis and abnormal dendrite arborization in CA1 neurons. These findings could indicate plastic changes related to epileptic activity in this area. Similar observations determined in experimental models of epilepsy, were related to inmature synapses and synapses reorganization.