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Distribution of carnosine-like peptides in the nervous system of developing and adult zebrafish (Danio rerio) and embryonic effects of chronic carnosine exposure


Carnosine-like peptides (carnosine-LP) are a family of histidine derivatives that are present in the nervous system of various species and that exhibit antioxidant, anti-matrix-metalloproteinase, anti-excitotoxic, and free-radical scavenging properties. They are also neuroprotective in animal models of cerebral ischemia. Although the function of carnosine-LP is largely unknown, the hypothesis has been advanced that they play a role in the developing nervous system. Since the zebrafish is an excellent vertebrate model for studying development and disease, we have examined the distribution pattern of carnosine-LP in the adult and developing zebrafish. In the adult, immunoreactivity for carnosine-LP is specifically concentrated in sensory neurons and non-sensory cells of the olfactory epithelium, the olfactory nerve, and the olfactory bulb. Robust staining has also been observed in the retinal outer nuclear layer and the corneal epithelium. Developmental studies have revealed immunostaining for carnosine-LP as early as 18 h, 24 h, and 7 days post-fertilization in, respectively, the olfactory, corneal, and retinal primordia. These data suggest that carnosine-LP are involved in olfactory and visual function. We have also investigated the effects of chronic (7 days) exposure to carnosine on embryonic development and show that 0.01 μM to 10 mM concentrations of carnosine do not elicit significant deleterious effects. Conversely, treatment with 100 mM carnosine results in developmental delay and compromised larval survival. These results indicate that, at lower concentrations, exogenously administered carnosine can be used to explore the role of carnosine in development and developmental disorders of the nervous system.

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We thank Dr. Howard Chang for the use of the Olympus BX51 fluorescence microscope and Siamak Hejabian for his contribution to cryostat sectioning. We are grateful to Drs. Jose Cibelli, Kannika Siripattarapravat, and Steven Suhr for helpful discussions and expertise. We appreciate the skillful assistance of Dr. Melinda Frame at the MSU Center for Advanced Microscopy. The Zebrafish International Resource Center is supported by an NIH-NCRR grant (no. P40 RR012546). The monoclonal antibody SV2 was obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by the University of Iowa, Department of Biological Sciences (Iowa City, USA).

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Correspondence to Marie-Claude Senut.

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This research was supported in part by an Intramural Research Grant Program Award from Michigan State University (no. 06-IRGP-899 to M.C.S.) and a grant from the National Institutes of Health (no. DC-03112 to F.L.M.).

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Senut, M., Azher, S., Margolis, F.L. et al. Distribution of carnosine-like peptides in the nervous system of developing and adult zebrafish (Danio rerio) and embryonic effects of chronic carnosine exposure. Cell Tissue Res 337, 45–61 (2009).

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  • Carnosine-like peptides
  • Nervous system
  • Development
  • Embryo toxicity
  • Zebrafish, Danio rerio (Teleostei)