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Chromogranin A (CgA) belongs to the family of chromogranin peptides which are contained in large dense-core vesicles. The novel CgA fragment catestatin (bovine CgA344–364; RSMRLSFRARGYGFRGPGLQL) is a potent inhibitor of catecholamine release by acting as a nicotinic cholinergic antagonist. Catestatin is a recently characterized neuropeptide, consisting of 21 amino acids, which might play an autocrine regulatory role in neuroendocrine secretion through its interaction with different nicotinic acetylcholine receptor subtypes. This study investigates for the first time the distribution of this peptide in the human auditory system using immunohistochemistry. A high density of catestatin-like immunoreactivity (catestatin-LI) is located in the spiral ganglion cells. In the dorsal cochlear nucleus, a high density of catestatin-LI consists of varicose fibers, immunoreactive varicosities and immunoreactive neurons. A moderate density is detected in the ventral cochlear and the medial vestibular nucleus. A low density is found in the inferior colliculus and superior olivary complex. The study indicates that catestatin is distinctly distributed in the auditory system, suggesting a role as a neuromodulatory peptide. Further studies should elucidate a possible interaction with other neurotransmitters in the auditory system. [Copyright &y& Elsevier]

The cochlear implant (CI) involves the introduction of alloplastic materials into the cochlea. While current implants interact with cochlear neurons at a distance, direct interactions between spiral ganglion (SG) neurites and implants could be fostered by appropriate treatment with neurotrophic factors. The interactions of fibroblasts and osteoblasts with alloplastic materials have been well studied in vitro and in vivo. However, interactions of inner ear neurons with such alloplastic materials have yet to be described. To investigate survival and growth behavior of SG neurons on different materials, SG explants from post-natal day 5 rat SG were cultured for 72 h in the presence of neurotrophin-3 (10 ng/ml) on titanium, gold, stainless steel, platinum, silicone and plastic surfaces that had been coated with laminin and poly-L-lysine. Neurite outgrowth was investigated after immunohistological staining for neurofilament, by image analysis to determine neurite extension and directional changes. Neurite morphology and adhesion to the alloplastic material were also evaluated by scanning electron microscopy (SEM). On titanium, SG neurites reached the highest extent of outgrowth, with an average length of 662 μm and a mean of 31 neurites per explant, compared to 568 μm and 21 neurites on gold, 574 μm and 24 neurites on stainless steel, 509 μm and 16 neurites on platinum, 281 μm and 12 neurites on silicone and 483 μm and 31 neurites on plastic. SEM revealed details of adhesion of neurites and interaction with non-neuronal cells. The results of this study indicate that the growth of SG neurons in vitro is strongly influenced by alloplastic materials, with titanium exhibiting the highest degree of biocompatibility with respect to neurite extension. The knowledge of neurite interaction with different alloplastic materials is of clinical interest, as development in CI technology leads to closer contact of implanted electrodes with surviving inner ear neurons. [Copyright &y& Elsevier]

Laminin-1 (LN) is expressed along the route of neural growth from spiral ganglion (SG) neurons towards the developing organ of Corti, and has been shown to enhance neurite outgrowth from SG neurons in vitro. Signal transduction pathways linking LN signaling at the cell membrane to the cell nucleus can involve a variety of signaling molecules. Data from other systems suggest the potential involvement of the small G protein Ras, and the mitogen-activated protein kinases (MAPKs) Erk and/or p38. To assess these possibilities, the length and number of processes extending from SG explants cultured on LN-coated surfaces were evaluated after treatment with the Ras inhibitor FTI-277, the p38 inhibitor SB203580 and MAPK kinase (MEK) inhibitor U0126, which operates immediately upstream of the Erk MAPK. Treatment with the Ras inhibitor at levels known to inhibit the H- and N-Ras isoforms had no effect, while FTI-277 levels known to inhibit K-Ras reduced only neurite length. Suppression of MEK resulted in a decrease of both parameters, while incubation with the p38 inhibitor had no effect. The results of this study suggest that MEK plays a central role in LN signaling in SG neurites. While K-Ras signaling may participate in MEK-dependent increases in neurite length, the MEK-dependent increase in neurite number appears to be activated by a different intracellular pathway. [ABSTRACT FROM AUTHOR]