Skip to Main content Skip to Navigation
Theses

Programmation foetale et plasticité cérébrale : conséquences d'une carence précoce en donneurs de méthyles chez le rat-impact à long terme d'un conditionnement hypoxique néonatal

Abstract : The alteration of homocysteine metabolism has been shown to constitute a risk factor for neurodegenerative diseases. Furthermore, whereas deleterious effects of severe neonatal hypoxia have been well documented, it was shown that a moderate episode of hypoxia can exert a neuroprotection with neurogenesis stimulation. Our main goal was to study the consequences on the brain of an early deficiency of methyl donors (folate, vitamin B12) with or without a hypoxia-related stimulation of neurogenesis. The effects of deficiency were investigated in rats born from dams fed a deficient diet until weaning. In vitro neuroprogenitors were additionally used for the study of cell mechanisms involved. Data showed alterations of tissue integrity in the hippocampus and the cerebellum, with associated behavioural deficits at various ages, despite a return to normal diet at weaning. Brain alterations were shown to be mainly related to epigenetic mechanisms and to homocysteinylation of specific neuronal proteins. Moreover, a sexual dimorphism was depicted, with the participation of ER alpha receptor. Neurogenesis induced in germinative zones by a brief neonatal hypoxia led to long term beneficial effects on brain aging in male rats, with preserved hippocampus integrity, in terms of cell density, synaptic plasticity, and related cognitive functions. Finally, the combination of deficiency and hypoxia revealed that brain conditioning by brief neonatal hypoxia was able to improve tissular and functional brain outcome in deficient rats. The key mechanisms involved would occur at critical periods during the maturation of the various brain structures, thus highlighting the role of fetal programming.
Document type :
Theses
Complete list of metadata

https://hal.univ-lorraine.fr/tel-01746239
Contributor : Thèses Ul <>
Submitted on : Thursday, March 29, 2018 - 10:28:35 AM
Last modification on : Tuesday, October 13, 2020 - 10:46:40 AM
Long-term archiving on: : Thursday, September 13, 2018 - 11:58:19 AM

File

SCD_T_2011_0091_MARTIN.pdf
Files produced by the author(s)

Identifiers

  • HAL Id : tel-01746239, version 1

Citation

Nicolas Martin. Programmation foetale et plasticité cérébrale : conséquences d'une carence précoce en donneurs de méthyles chez le rat-impact à long terme d'un conditionnement hypoxique néonatal. Médecine humaine et pathologie. Université Henri Poincaré - Nancy 1, 2011. Français. ⟨NNT : 2011NAN10091⟩. ⟨tel-01746239⟩

Share

Metrics

Record views

93

Files downloads

1938