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Exploration de la plasticité neuronale et gliale dans le système à mélanocortine à l'échelle des repas dans un modèle murin.

Abstract : In 2015, Nature published the largest pangenomic association study to date linking genetic variants to body mass index. This study highlighted the role of the central nervous system in vulnerability to obesity and supports an original concept that cerebral plasticity plays an important role in the control of energy balance. Thus, reduced cerebral plasticity capacities could lead to inadequate dietary behaviors, which would increase the risk of weight gain under caloric pressure. The anorectic neurons POMC and the orexigenic neurons AgRP of the melanocortin system, which control the energy balance, actually show synaptic plasticity properties in the adult brain. These phenomena are shown in response to intense hormonal fluctuations induced by drastic genetic, surgical or nutritional manipulations. However, the physiological role of this synaptic plasticity within the melanocortin system has not been demonstrated yet. This study shows that cerebral plasticity phenomena are recapitulated at the meal scale in mice, depending on the prandial state, in response to moderate metabolic and hormonal changes. Indeed, 1 h standard diet exposure increases the electrical activity of the POMC neurons, which is correlated with a retraction of the astrocytic coverage around the POMC somas, with no change in synaptic configuration compared to the preprandial state. In contrast, 1 hour of high fat diet exposure does not modify the electrical activity of the POMC neurons and does not involve retraction of the astrocytic coverage. In addition, by pharmacological blockade of postprandial hyperglycemia, we showed that glucose is required for postprandial glial retraction. Finally, by a pharmacogenetic approach, we have shown that the inactivation of astrocytes modifies the feeding behavior and decreases the astrocytic coverage around the POMC neurons. These results suggest i)that astrocytes would play an inhibitory role on the electrical activity of POMC neurons ii) and that the post-prandial astrocytic retraction around POMC somas might remove inhibition of POMC neurons and might promote the sensation of satiety. This mode of regulation would not be activated during a high-fat meal, which would explain the low satietogenic properties of this type of meal.
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https://tel.archives-ouvertes.fr/tel-01781293
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Submitted on : Monday, April 30, 2018 - 9:40:06 AM
Last modification on : Wednesday, September 5, 2018 - 5:04:05 PM
Long-term archiving on: : Tuesday, September 25, 2018 - 7:34:58 PM

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Danaé Nuzzaci. Exploration de la plasticité neuronale et gliale dans le système à mélanocortine à l'échelle des repas dans un modèle murin.. Physiologie [q-bio.TO]. Université Bourgogne Franche-Comté, 2017. Français. ⟨NNT : 2017UBFCK037⟩. ⟨tel-01781293⟩

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