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A Peptidomic Approach to Characterize Peptides Involved in Cerebellar Cortex Development Leads to the Identification of the Neurotrophic Effects of Nociceptin

Auriane Corbière 1 Marie-Laure Walet-Balieu 2 Philippe Chan 2 Magali Basille-Dugay 1 Julie Hardouin 2 David Vaudry 2, 1, 3 
2 Plate-forme de Protéomique PISSARO
IRIB - Institute for Research and Innovation in Biomedicine, HeRacLeS - High-tech Research Infrastructures for Life Sciences
3 PRIMACEN - Plate-Forme de Recherche en Imagerie Cellulaire de Haute-Normandie
UNIROUEN - Université de Rouen Normandie, IRIB - Institute for Research and Innovation in Biomedicine, HeRacLeS - High-tech Research Infrastructures for Life Sciences
Abstract : The cerebellum is a brain structure involved in motor and cognitive functions. The development of the cerebellar cortex (the external part of the cerebellum) is under the control of numerous factors. Among these factors, neuropeptides including PACAP or somatostatin modulate the survival, migration and/or differentiation of cerebellar granule cells. Interestingly, such peptides contributing to cerebellar ontogenesis usually exhibit a specific transient expression profile with a low abundance at birth, a high expression level during the developmental processes, which take place within the first two postnatal weeks in rodents, and a gradual decline toward adulthood. Thus, to identify new peptides transiently expressed in the cerebellum during development, rat cerebella were sampled from birth to adulthood, and analyzed by a semi-quantitative peptidomic approach. A total of 33 peptides were found to be expressed in the cerebellum. Among these 33 peptides, 8 had a clear differential expression pattern during development, 4 of them i.e. cerebellin 2, nociceptin, somatostatin and VGF [353-372], exhibiting a high expression level during the first two postnatal weeks followed by a significative decrease at adulthood. A focus by a genomic approach on nociceptin, confirmed that its precursor mRNA is transiently expressed during the first week of life in granule neurons within the internal granule cell layer of the cerebellum, and showed that the nociceptin receptor is also actively expressed between P8 and P16 by the same neurons. Finally, functional studies revealed a new role for nociceptin, acting as a neurotrophic peptide able to promote the survival and differentiation of developing cerebellar granule neurons.
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Submitted on : Wednesday, February 2, 2022 - 5:40:04 PM
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Auriane Corbière, Marie-Laure Walet-Balieu, Philippe Chan, Magali Basille-Dugay, Julie Hardouin, et al.. A Peptidomic Approach to Characterize Peptides Involved in Cerebellar Cortex Development Leads to the Identification of the Neurotrophic Effects of Nociceptin. Molecular and Cellular Proteomics, 2018, 17 (9), pp.1737-1749. ⟨10.1074/mcp.RA117.000184⟩. ⟨hal-03553428⟩

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