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Effets de la carence en vitamine B12 au niveau cérébral chez le modèle murin invalidé pour le gène CD320 : approche comportementale et mécanismes moléculaires de l'apprentissage hippocampo-dépendant

Abstract : It is now clearly established that vitamin B12 (or cobalamin), plays an important role in the formation of red blood cells, as well as it has a vital role in the efficient functioning of the nervous system such as cognitive functions. Vitamin B12 deficiency is widespread worldwide and causes megaloblastic anemia and neurological deficits. Vitamin B12 deficiency and the hyperactivity of the glucocorticoid (GC) contribute to the deterioration of hippocampal plasticity and functions. To understand whether cobalamin deficiency in the central nervous system produced functional neurologic deficits, we used a transcobalamin receptor / CD320 knockout mouse that lacks the receptor for the cellular uptake of cobalamin in the brain. Our behavioral analyses indicate deficits in hippocampo-dependant visuo-spatial learning capacities in KO mice. However, a daily physiological dose of hydroxycortisone (8 mg/kg/day I.P.) has a positive effect in improving learning performances in KO mice compared to controls. Consistent with the behavioral deficits, the knockout mouse shows impaired expression of key proteins implicated in synaptic plasticity. The results of western blot analyses of hippocampus extracts revealed that the knockout female mice showed decreased expressions of glucocorticoids receptors (GR), Peroxisome proliferator-activated receptor coactivator 1 (PGC-1), early growth response protein -1 (EGR-1), Synapsines (Syn I, II), Protein arginine N-methyltransferase -1 (PRMT-1), key proteins known to be implicated in the synaptic activity. The study of the CD320 knock out model could help to better understand the effects of vitamin B12 deficiency observed in humans, in order to identify potential responses to various neurological associated disorders; with a putative palliative treatment approach using corticoids
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Khalid Mimoun. Effets de la carence en vitamine B12 au niveau cérébral chez le modèle murin invalidé pour le gène CD320 : approche comportementale et mécanismes moléculaires de l'apprentissage hippocampo-dépendant. Médecine humaine et pathologie. Université de Lorraine, 2017. Français. ⟨NNT : 2017LORR0262⟩. ⟨tel-01822463⟩

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