Chromogranins as markers of altered hippocampal circuitry in temporal lobeepilepsy

Chromogranins are polypeptides which are widely expressed in the central ne rvous system. They are stored in dense core vesicles of nerve terminals, fr om where they are released upon stimulation. Using immunocytochemistry, we investigated the distribution of chromogranin A, chromogranin B, sccretoneu rin, and, for comparison, dynorphin in hippocampal specimens removed at rou tine surgery from patients with drug-resistant mesial temporal lobe epileps y and in autopsy tissues from nonneurologically deceased subjects. In post mortem controls (n = 21), immunoreactivity for all 4 peptides (most promine ntly for chromogranin B and dynorphin) was observed in the terminal field o f mossy fibers. For chromogranins, staining was observed also in sectors CA I to CA3 and in the subiculum. Chromogranin B immunoreactivity was found in the inner molecular layer of the dentate gyrus, the area of terminating as sociational-commissural fibers. Secretoneurin and dynorphin immunoreactivit y labeled the outer molecular layer and the stratum lacunosum moleculare of sectors CAI to CA3, where projections from the entorhinal cortex terminate . In specimens with Ammon's horn sclerosis (n = 25), staining for all 3 chr omogranins and for dynorphin was reduced in the hilus of the dentate gyrus. Instead, intense staining was observed in the inner molecular layer, presu mably delineating terminals of sprouted mossy fibers. Specimens obtained fr om temporal lobe epilepsy patients without Ammon's horn sclerosis (n = 4) l acked this pronounced rearrangement of mossy fibers. In the stratum lacunos um moleculare of sector CAI, secretoneurin and dynorphin immunoreactivity w as reduced in sclerotic, but not in nonsclerotic, specimens, paralleling th e partial loss of fibers arising from the entorhinal cortex. Instead, presu mably sprouted secretoneurin-immunoreactive fibers were found in the outer dentate molecular layer in sclerotic specimens. These changes in staining p atterns for chromogranins and dynorphin mark profound plastic and functiona l rearrangement of hippocampal circuitry in temporal lobe epilepsy.