Skip to Main content Skip to Navigation
Theses

Etude du peptidome du cervelet de rat au cours du développement et identification des effets neurotrophiques de la nociceptine dans la mise en place des neurones en grain.

Abstract : The cerebellum is a structure involved in many motor and cognitive functions whose development occurs after birth under the control of various factors, including neuropeptides. Peptides acting on cerebellar cortex development often exhibit a specific pattern of expression with in rodents a high expression over the 2 first postnatal weeks which then decreases at adulthood. The aim of this study was to identify additional peptides with such expression profile and to characterize their putative functions in the development of the cerebellar cortex and more particularly, in the establishment of cerebellar granule neurons which are the most abundant cells of the cerebellum. To address this, cerebella of rats aged from 8 to 90 days-old were analyzed by mass spectrometry. Among the 33 peptides identified in the cerebellum, 4 had the particular expression profile we were looking for. We choose to study further one of them, i.e. the nociceptin, and confirmed peptidomic results by measuring the expression of its gene precursor and of its receptor. Combining laser microdissection and qPCR approaches revealed that both nociceptin and its receptor genes were expressed in the internal granular layer of the cerebellar cortex. Functional studies showed that nociceptin exerts a neurotrophic effect on granule neurons by increasing their survival and differentiation, but had no effect on their motility. Preliminary in vivo experiments indicate that nociceptin can also counteract ethanol-induced toxicity. The last part of the present study aimed to identify new neuropeptides expressed in the rat cerebellum by using de novo sequencing. The large amount of peptide sequences initially found was then reduced to only 6 candidates for further analysis, by using filters such as recurrence of the sequences and their differential expression in between the four developmental stages considered. Additional genomic studies will help to decrease even further this number, in order to focus the biological tests on the targets which are most likely to code for biological active peptides.
Document type :
Theses
Complete list of metadatas

https://tel.archives-ouvertes.fr/tel-01819085
Contributor : Abes Star :  Contact
Submitted on : Wednesday, June 20, 2018 - 1:01:51 AM
Last modification on : Tuesday, April 7, 2020 - 3:36:03 PM
Long-term archiving on: : Tuesday, September 25, 2018 - 5:12:24 PM

File

corbiereauriane2.pdf
Version validated by the jury (STAR)

Identifiers

  • HAL Id : tel-01819085, version 1

Citation

Auriane Corbière. Etude du peptidome du cervelet de rat au cours du développement et identification des effets neurotrophiques de la nociceptine dans la mise en place des neurones en grain.. Biologie du développement. Normandie Université, 2017. Français. ⟨NNT : 2017NORMR063⟩. ⟨tel-01819085⟩

Share

Metrics

Record views

276

Files downloads

435