Conséquences d'une carence en donneurs de méthyles sur la différenciation cellulaire, la survie et la neuroplasticité : approches mécanistiques in vitro sur des lignées neuronales

Abstract : Folate (vitamin B9) and vitamin B12 act as cofactors in the one-carbon metabolism that regulates transmethylation reactions involved in epigenetic mechanisms. A deficiency in folate and/or B12 decreases the generation of methionine from homocysteine, a toxic amino acid that has been associated with pathologies of the central nervous system at all ages (spina bifida, Alzheimer's disease...). In order to depict the cellular and molecular mechanisms implicated in the response to the deficiency in these micronutrients, two new cell models have been developed. Thus, we have analyzed the effects of folate deficiency on proliferation, differentiation and neuroplasticity of neuronal progenitors obtained from the hippocampus of rat embryos, i.e. the H19-7 cell line. Regarding the second model, we designed an original approach by stable transfection of NIE-115 murine neuroblastoma cells to impose the anchorage of a chimeric B12 binding protein, transcobalaminoleosin (TO) to intracellular membrane in order to produce intracellular sequestration of B12. Taken together, our results have shown that deficiency-associated alterations of the one-carbon metabolism lead to reduced neurogenesis and to dramatic impairment of neuron differentiation. This suggests the existence of specific mechanisms through which vitamin B9/B12 deficiency and/or homocysteine may affect brain functioning and plasticity.
Complete list of metadatas

https://hal.univ-lorraine.fr/tel-01748296
Contributor : Thèses Ul <>
Submitted on : Thursday, March 29, 2018 - 11:30:55 AM
Last modification on : Monday, April 16, 2018 - 10:41:48 AM
Long-term archiving on : Friday, September 14, 2018 - 12:29:23 AM

File

SCD_T_2009_0122_AKCHICHE.pdf
Files produced by the author(s)

Identifiers

  • HAL Id : tel-01748296, version 1

Collections

Citation

Nassila Akchiche. Conséquences d'une carence en donneurs de méthyles sur la différenciation cellulaire, la survie et la neuroplasticité : approches mécanistiques in vitro sur des lignées neuronales. Médecine humaine et pathologie. Université Henri Poincaré - Nancy 1, 2009. Français. ⟨NNT : 2009NAN10122⟩. ⟨tel-01748296⟩

Share

Metrics

Record views

18

Files downloads

53