Chromogranins in temporal lobe epilepsy

Purpose: Chromogranins are neuropeptide precursors stored in large dense co re vesicles. Because physiological functions have been postulated for pepti des originating from chromogranins, we investigated the distribution of chr omogranins A and B and secretoneurin (a peptide derived from secretogranin II) in the control and epileptic hippocampus of humans and rats. Methods: Chromogranin immunoreactivity (LR) was investigated in paraformald ehyde-fixed hippocampal specimens from 24 temporal lobe epilepsy patients w ith intractable seizures, postmortem from 15 patients deceased from nonneur ological disorders, in rats 30 days after kainate-induced limbic seizures, and in control rats. Results: In control rats and in humans, chromogranin A and B IR and secreto neurin IR were present in mossy fibers. In addition, chromogranin B IR was found in granule cells, and chromogranin A IR was found in granule and CA2 pyramidal cells in the human hippocampus. In both species, chromogranin B a nd secretoneurin were unevenly distributed in the molecular layer of the de ntate gyrus. The most intriguing change seen in human temporal lobe epileps y specimens and in the kainic acid model of the rat was the prominent stain ing of the inner molecular layer, indicating storage of chromogranins A and B and secretoneurin in terminals of reorganized mossy fibers, from which t hey may be released upon nerve stimulation. Conclusion: Chromogranins A and B and secretoneurin are valid markers for h ippocampal neurons and delineate epilepsy-induced reorganization of mossy f ibers.