Chromogranins in Temporal Lobe Epilepsy

Abstract

Summary:Purpose: Chromogranins are neuropeptide precursors stored in large dense core vesicles. Because physiological functions have been postulated for peptides originating from chromogranins, we investigated the distribution of chromogranins A and B and secretoneurin (a peptide derived from secretogranin 11) in the control and epileptic hippocampus of humans and rats.Methods: Chromogranin immunoreactivity (IR) was investigated in paraformaldehyde-fixed hippocampal specimens from 24 temporal lobe epilepsy patients with intractable seizures, postmortem from 15 patients deceased from nonneurological 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 secretoneurin 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 and secretoneurin were unevenly distributed in the molecular layer of the dentate gyrus. The most intriguing change seen in human temporal lobe epilepsy specimens and in the kainic acid model of the rat was the prominent staining of the inner molecular layer, indicating storage of chromogranins A and B and secretoneurin in terminals of reorganized mossy fibers, from which they may be released upon nerve stimulation. Chromogranins are acidic polypeptides with a wide distribution in the nervous and endocrine systems. They are named for their first isolation in secretory granules of chromaffine cells in the adrenal medulla (1). Members of this family are chromogranin A (CgA), chromogranin B (CgB), and secretogranin 11. They are stored in large dense core vesicles in which they are processed to smaller peptides (e.g., secretogranin I1 is processed to secretoneurin). Like classic neuropeptides, chromogranins are thought to be released upon neuronal stimulation and may exert their physiological functions at that time. Conclusion: ChromograninsIn the kainic acid model of temporal lobe epilepsy (TLE), marked changes in CgA and CgB messenger RNA (mRNA) levels were observed in granule cells of the dentate gyrus and in secretogranin I1 mRNA in pyramidal cells (2,3), suggesting a role for chromogranins in experimental epilepsy.There are limited data available on the distribution of chromogranins, on the protein level in the rat and human hippocampus, and on epilepsy-induced alterations (4-9). The goal of the present study was to investigate changes Address correspondence and reprint requests to Dr. Susanne Kandlhofer at Department of Neurosurgery, University of Vienna, Wahringer Gurtel 18-20, A-1090 Vienna, Austria. E-mail: susanne.pirker@univie.ac.at in the distribution of chromogranins in the kainic acid model and in surgical specimens of TLE patients and to evaluate chromogranins as possible markers for hippocampal structures. MATERIALS AND METHODS The kainic acid model of temporal lobe epilepsyRats were injected with kainic acid (KA; 10 mgkg intrap...

The impact of postsynaptic density 95 blocking peptide (Tat‐NR2B9c) and an iNOS inhibitor (1400W) on proteomic profile of the hippocampus in C57BL/6J mouse model of kainate‐induced epileptogenesis

“…Likewise, vimentin, an intermediate filament protein that co‐localizes with GFAP in reactive astrocytes (Sancho‐Tello, Vallés, Montoliu, Renau‐Piqueras, & Guerri, ), is elevated in seizures associated with angiocentric glioma (Ni et al, ) and is also considered to be a marker of the astrogliosis seen in tuberous sclerosis (Sosunov et al, ). A change in abundance of Src substrate cortactin is consistent with the involvement of Src kinases and neuroinflammation in epileptogenesis, which we have demonstrated previously (Sharma et al, ), while secretogranin‐2 is up‐regulated following experimental seizures, particularly with KA, in a distinctive cell‐type and species specific manner (Kandlhofer et al, ; Mahata et al, ; Marti, Blasi, & Ferrer, ).…”

Immunohistochemical field parcellation of the human hippocampus along its antero-posterior axis

“…They are also essential to vesicle filling (Dominguez et al 2018 ). ChrA in human hippocampus is present in CA2 pyramidal cells, granule cells and mossy fibers (Kandlhofer et al 2000 ). A purified IgG monoclonal anti-chromogranin A antibody was used in this study (Wilson and Lloyd 1984 ; LK2H10, Cell Marque ® ).…”

Secretoneurin in the Peripheral Ocular Innervation

“…1,8 SN is highly conserved during evolution and found in mammals, birds, amphibians, and fish. 9 It is distinctly distributed throughout the central nervous system, both in humans 10 -14 and rats [15][16][17][18][19][20] and is released from brain tissue in a Ca 2ϩdependent manner. 21 To date, several biological activities have been established for SN.…”