Conséquence d'une carence gestationnelle en donneurs de méthyles sur l'expression des protéines clés de la neurostéroïdogenèse chez le rat

Abstract : Early methyl-donor deficiency (MDD, folate and vitamin B12) produces hyperhomocysteinemia, cognitive and motor disorders in 21 days-old rat pups. These disorders are linked to an alteration of neurogenesis in the cerebellum and the hippocampus, which is closely linked to neurosteroidogenesis, defined as the local synthesis of steroids in brain. The aim of this work was to verify if these troubles are associated with an altered neurosteroidogenesis. This work led to several striking results, showing in particular the deleterious effects of the methyl donor deficiency on the steroidogenic pathway in the cerebellum, particularly vulnerable during postnatal development. This was confirmed by the reduced contents of estradiol and other neurosteroids, as a result of the decrease of the expression of StAR, TSPO and aromatase, as well as the estrogen receptors. These deleterious effects are associated to the impairment of AMPc dependent signaling pathway and the decrease of transcription factors, notably SF-1, which the presence in the cerebellar Purkinje cells had never been described previously. This response to the deficiency would be made according to a sexual dimorphism, since only the young deficient females were affected. Finally, these studies allowed us to show functional changes associated with the cellular and molecular damage observed in the olfactory bulbs, being traduced by a decrease of the olfactory discrimination. This could contribute to the growth retardation associated with the reduced body weight of the deficient animals
Document type :
Theses
Complete list of metadatas

https://hal.univ-lorraine.fr/tel-01750343
Contributor : Thèses Ul <>
Submitted on : Thursday, March 29, 2018 - 12:43:28 PM
Last modification on : Monday, April 23, 2018 - 3:53:37 PM

File

DDOC_T_2013_0163_EL_CHAKOUR.pd...
Files produced by the author(s)

Identifiers

  • HAL Id : tel-01750343, version 1

Collections

Citation

Sarah El Chakour El Hajj Chehadeh. Conséquence d'une carence gestationnelle en donneurs de méthyles sur l'expression des protéines clés de la neurostéroïdogenèse chez le rat. Médecine humaine et pathologie. Université de Lorraine, 2013. Français. ⟨NNT : 2013LORR0163⟩. ⟨tel-01750343⟩

Share

Metrics

Record views

40

Files downloads

53