Skip to Main content Skip to Navigation
Theses

Impact de l'apport alimentaire en AGPI n-3 sur le métabolisme énergétique cérébral : approches in vivo chez le rat en situation de repos ou d'activation neuronale et in vitro sur un modèle d'astrocytes en culture primaire

Abstract : Cerebral energy metabolism via glucose utilization is heavily involved in the production of energy required to the neuron in basal conditions and activation. Previous work has shown in rats chronically deficient in n-3 polyunsaturated fatty acids (PUFA) altered the metabolism in basal condition (decrease of cerebral glucose use and density of glucose transporters GLUT1). To identify the different stages of energy metabolism may be modified by n-3 PUFA, the expression of key genes was measured by transcriptomic approach (Taqman Low Density Arrays) in animals deficient in n-3 PUFA or docosahexaenoic acid supplementation (DHA, 22:6n-3). These measurements were performed on two brain areas (fronto-parietal cortex and layer CA1 of the hippocampus) in animals in basal condition or submit to an enriched environment. For these two situations, the level of cerebral glucose utilization was quantified by the technique of fluoro-2-deoxyglucose imaging coupled with positron emission tomography (18FDG-PET) only in deficient n-3 PUFA animals. Analysis of brain PUFA content of membrane was performed by gas chromatography and an in vitro approach to primary culture of astrocytes was developed to assess the impact of DHA on metabolic parameters of these cells.The main results show that: - n-3 Deficiency decreases from 67% in membrane DHA content in both brain areas studied. If the deficiency induces mainly a decrease in the specific expression of GLUT1 (-33%) in the fronto-parietal cortex in basal and activation conditions, however it disrupts glutamatergic neurotransmission in the hippocampus by increasing the expression of two glutamate transporters (GLAST and GLT1). In addition, PET data show a general hypometabolism of glucose in animals deficient in n-3 in basal situation. Data collected on the model astrocytes point to a direct effect of DHA on glucose utilization and expression of GLUT1; -DHA supplementation does not alter significantly the membrane content of DHA in both brain areas studied. Unlike the n-3 deficiency, it is clear for the layer CA1 of the hippocampus that the expression of all genes encoding the enzyme complexes of the Krebs cycle and oxidative phosphorylation pathway is significantly increased. These original results suggest the possibility that the fatty acids of the n-3 PUFAs family can act on the energy and functioning of the glutamatergic synapse by modulating 1) glucose metabolism (glucose uptake) and glutamate in deficit intake situation and 2) the production of ATP (oxidative phosphorylation) in DHA supplementation. The alteration of these metabolic parameters during aging and certain neurological disorders, related to a deficit of DHA status, highlight the potential of dietary n-3 PUFA as a preventive factor.
Document type :
Theses
Complete list of metadatas

Cited literature [218 references]  Display  Hide  Download

https://tel.archives-ouvertes.fr/tel-00653444
Contributor : Abes Star :  Contact
Submitted on : Monday, December 19, 2011 - 3:08:36 PM
Last modification on : Friday, October 23, 2020 - 5:04:18 PM
Long-term archiving on: : Tuesday, March 20, 2012 - 2:32:03 AM

File

VA_HARBEBY_EMILIE_26092011.pdf
Version validated by the jury (STAR)

Identifiers

  • HAL Id : tel-00653444, version 1
  • PRODINRA : 245818

Collections

Citation

Emilie Harbeby. Impact de l'apport alimentaire en AGPI n-3 sur le métabolisme énergétique cérébral : approches in vivo chez le rat en situation de repos ou d'activation neuronale et in vitro sur un modèle d'astrocytes en culture primaire. Sciences agricoles. Université Paris Sud - Paris XI, 2011. Français. ⟨NNT : 2011PA112160⟩. ⟨tel-00653444⟩

Share

Metrics

Record views

752

Files downloads

1382