WorldCat Identities

Cota, Daniela

Overview
Works: 17 works in 17 publications in 2 languages and 20 library holdings
Roles: Opponent, Thesis advisor, Contributor, Other
Publication Timeline
.
Most widely held works by Daniela Cota
Toward a new computer-based and easy-to-use tool for the objective measurement of motivational states in humans: a pilot study by Bruno Aouizerate( )

1 edition published in 2014 in English and held by 2 WorldCat member libraries worldwide

Sequential alteration of microglia and astrocytes in the rat thalamus following spinal nerve ligation by Lucie Blaszczyk( )

1 edition published in 2018 in English and held by 2 WorldCat member libraries worldwide

Obesity and the Endocannabinoid System: Circulating Endocannabinoids and Obesity by Isabelle Matias( )

1 edition published in 2012 in English and held by 2 WorldCat member libraries worldwide

Rôle du récepteur aux cannabinoïdes de type 1 (CB1) hypothalamique dans la régulation de la balance énergétique et de l'homéostasie du glucose by Pierre Cardinal( )

1 edition published in 2013 in French and held by 1 WorldCat member library worldwide

The endocannabinoid system is a major player in energy balance regulation. However, a complete understanding of its role within the hypothalamus, a region critically involved in energy balance regulation, is still missing. The general aim of this PhD work was to dissect the specific role of the cannabinoid type 1 receptor (CB1) expressed on different hypothalamic neuronal populations in energy balance regulation and glucose homeostasis by characterizing three new mouse mutant lines with a conditional deletion of CB1. On standard diet, CB1 deletion within the hypothalamus induced an increase in energy expenditure and a decrease in body weight gain without modifying food intake, while CB1 deletion within the ventromedial nucleus of the hypothalamus (VMN-CB1-KO) decreased fat mass, increased fatty acid oxidation in vivo and sympathetic nervous system (SNS) activity, and improved peripheral glucose metabolism. CB1 deletion within the paraventricular nucleus of the hypothalamus (PVN-CB1-KO) decreased body weight gain without affecting food intake or body composition. When exposed to a high-fat diet, VMN-CB1-KO mice gained significantly more weight and fat mass than their WT, while PVN-CB1-KO mice were partly protected from diet-induced obesity thanks to increased energy expenditure. These results overall suggest that CB1 expressed on different hypothalamic neuronal populations have distinct roles in energy balance regulation, which in turn also depend on the diet consumed
Rôle des récepteurs sérotoninergique2B centraux dans la régulation des voies dopaminergiques ascendantes : implication dans les effets de la cocaïne by Adeline Cathala( )

1 edition published in 2021 in French and held by 1 WorldCat member library worldwide

My study on the functional role of the central serotoninergic receptor2B (5-HT2BR) is a logical continuation of the work already carried out in the laboratory. Recent results obtained in the laboratory have shown that 5-HT2BRs differentially modulate ascending dopaminergic (DA) pathways. Indeed, 5-HT2BR antagonist reduces DA release in the nucleus accumbens (NAc), increases DA release in the medial prefrontal cortex (mPFC), and had no effect on striatal DA release. This differential control on the DA system involves an interaction between 5-HT2BR in the dorsal raphe nucleus (DRN) and 5-HT1AR expressed in the mPFC, and results from an activation of DRN 5-HT neurons projecting to the mPFC. These results point out the DRN as the major site of action of 5-HT2BRs to the control of 5-HT and DA activity. In addition, it has been shown that 5-HT2BRs blockade control the neurochemical and behavioral responses induced by psychostimulants as amphetamine, 3,4-methylenedioxymethamphetamine and cocaine, one of the most worldwide abused drugs. Indeed, 5-HT2BR blockade suppresses cocaine-induced hyperlocomotion. This effect, which occurs independently of DA release in the NAc and striatum, where DA activity is tightly related to cocaine-induced behavioral reponses, likely involves post-synaptic interaction in subcortical DA brain regions. Nevertheless, (1) the involvement of mPFC DA release in this interaction remained to be determined, as this brain region is known for its anatomical and functional relationships with the NAc and striatum, and its involvement in cocaine-induced behavioral responses. (2) In addition, the cellular localization of 5-HT2BR within the DRN and the cellular mechanisms underlying their interactions between DA and 5-HT networks are unknown at the beginning of this study. Thus, the objective of this thesis is to answer the two points mentioned above. To this purpose, we assessed the effects of two potent and selective 5-HT2BR antagonists (RS 127445 and LY 266097) on 5-HT and DA activity, by using neurochemical, cellular and behavioral approaches in rats.In a first group of experiments, we provided anatomo-functional evidences showing that 5-HT2BR exert a GABA-mediated tonic inhibitory control on DRN 5-HT neurons innervating mPFC. This 5-HT control is a first step of a complex poly-synaptic regulation leading to differential control of DA mesocorticolimbic pathways. A second group of experiments shown that 5-HT2BR blockade inhibits cocaine-induced hyperlocomotion by acting at the level of DA neurotransmission in NAc, this effect resulting from the potentiation of cocaine-induced mPFC DA release.To conclude, the work accomplished over the past three years provides substantial information with regards to the functional role of 5-HT2BRs in the regulation of the activity of ascending DA pathways. Moreover, while improving the understanding of the interaction between DA and 5-HT systems, the present findings altogether highlight the therapeutic potential of 5-HT2BR antagonists for the treatment of cocaine addiction
Endocannabinoid modulation of homeostatic and non-homeostatic feeding circuits( )

1 edition published in 2017 in English and held by 1 WorldCat member library worldwide

Abstract: The endocannabinoid system has emerged as a key player in the control of eating. Endocannabinoids, including 2-arachidonoylglycerol (2-AG) and anandamide (AEA), modulate neuronal activity via cannabinoid 1 receptors (CB1Rs) in multiple nuclei of the hypothalamus to induce or inhibit food intake depending on nutritional and hormonal status, suggesting that endocannabinoids may act in the hypothalamus to integrate different types of signals informing about the animal's energy needs. In the mesocorticolimbic system, (endo)cannabinoids modulate synaptic transmission to promote dopamine release in response to palatable food. In addition, (endo)cannabinoids act within the nucleus accumbens to increase food's hedonic impact; although this effect depends on activation of CB1Rs at excitatory, but not inhibitory inputs in the nucleus accumbens. While hyperactivation of the endocannabinoid system is typically associated with overeating and obesity, much evidence has emerged in recent years suggesting a more complicated system than first thought - endocannabinoids promote or suppress feeding depending on cell and input type, or modulation by various neuronal or hormonal signals. This review presents our latest knowledge of the endocannabinoid system in non-homeostatic and homeostatic feeding circuits. In particular, we discuss the functional role and cellular mechanism of action by endocannabinoids within the hypothalamus and mesocorticolimbic system, and how these are modulated by neuropeptide signals related to feeding. In light of recent advances and complexity in the field, we review cannabinoid-based therapeutic strategies for the treatment of obesity and how peripheral restriction of CB1R antagonists may provide a different mechanism of weight loss without the central adverse effects. This article is part of the Special Issue entitled "A New Dawn in Cannabinoid Neurobiology". Graphical abstract: Endocannabinoid modulation of the mesocorticolimbic and hypothalamic circuits: a highly interconnected circuit of excitatory (glutamatergic) and inhibitory (GABAergic) pathways exist between the ventral tegmental area (VTA), nucleus accumbens (NAc), medial prefrontal cortex (mPFC) and hypothalamus (Hyp). Furthermore, the VTA sends prominent dopamine projections to the NAc and mPFC. A number of synaptic inputs onto principal neurons within the VTA (dopamine neurons), NAc (medium spiny neurons), mPFC (pyramidal neurons) and hypothalamus express CB1 receptors, and are sensitive to endocannabinoid-mediated, short-term plasticity (DSI/DSE) and/or long-term plasticity (LTD/iLTD) in naive animals. Exposure to a palatable/high-fat diet (or omega-3 deficient diet) or the development of diet-induced obesity can alter these forms of synaptic plasticity [Insets:+/− indicates present/absent, while ↑/↓/=/? indicate increase/decrease/no change/unknown, respectively]. Highlights: Endocannabinoids act in multiple hypothalamic nuclei to integrate signals informing about the animal's energy needs. Endocannabinoids modulate synaptic transmission in the VTA and NAc to promote dopamine release in response to palatable food. Peripherally restricted cannabinoid receptor antagonists may be therapeutic in the treatment of obesity
Bases neurobiologiques des troubles de l'humeur et de la cognition associés à l'obésité : rôle de l'inflammation by Celia Fourrier( )

1 edition published in 2016 in French and held by 1 WorldCat member library worldwide

Nutritional status-dependent endocannabinoid signalling regulates the integration of rat visceral information( )

1 edition published in 2017 in English and held by 1 WorldCat member library worldwide

Abstract : Key points: Vagal sensory inputs transmit information from the viscera to brainstem neurones located in the nucleus tractus solitarii to set physiological parameters. These excitatory synapses exhibit a CB1 endocannabinoid-induced long-term depression (LTD) triggered by vagal fibre stimulation. We investigated the impact of nutritional status on long-term changes in this long-term synaptic plasticity. Food deprivation prevents LTD induction by disrupting CB1 receptor signalling. Short-term refeeding restores the capacity of vagal synapses to express LTD. Ghrelin and cholecystokinin, respectively released during fasting and refeeding, play a key role in the control of LTD via the activation of energy sensing pathways such as AMPK and the mTOR and ERK pathways. Abstract: Communication form the viscera to the brain is essential to set physiological homoeostatic parameters but also to drive more complex behaviours such as mood, memory and emotional states. Here we investigated the impact of the nutritional status on long-term changes in excitatory synaptic transmission in the nucleus tractus solitarii, a neural hub integrating visceral signals. These excitatory synapses exhibit a CB1 endocannabinoid (eCB)-induced long-term depression (LTD) triggered by vagal fibre stimulation. Since eCB signalling is known to be an important component of homoeostatic regulation of the body and is regulated during various stressful conditions, we tested the hypothesis that food deprivation alters eCB signalling in central visceral afferent fibres. Food deprivation prevents eCB-LTD induction due to the absence of eCB signalling. This loss was reversed by blockade of ghrelin receptors. Activation of the cellular fuel sensor AMP-activated protein kinase or inhibition of the mechanistic target of rapamycin pathway abolished eCB-LTD in free-fed rats. Signals associated with energy surfeit, such as short-term refeeding, restore eCB-LTD induction, which in turn requires activation of cholecystokinin receptors and the extracellular signal-regulated kinase pathway. These data suggest a tight link between eCB-LTD in the NTS and nutritional status and shed light on the key role of eCB in the integration of visceral information. Key points: Vagal sensory inputs transmit information from the viscera to brainstem neurones located in the nucleus tractus solitarii to set physiological parameters. These excitatory synapses exhibit a CB1 endocannabinoid-induced long-term depression (LTD) triggered by vagal fibre stimulation. We investigated the impact of nutritional status on long-term changes in this long-term synaptic plasticity. Food deprivation prevents LTD induction by disrupting CB1 receptor signalling. Short-term refeeding restores the capacity of vagal synapses to express LTD. Ghrelin and cholecystokinin, respectively released during fasting and refeeding, play a key role in the control of LTD via the activation of energy sensing pathways such as AMPK and the mTOR and ERK pathways
Rôle(s) du récepteur aux cannabinoïdes mitochondrial de type 1 dans le cerveau by Tifany Desprez( )

1 edition published in 2015 in English and held by 1 WorldCat member library worldwide

Rôle de la néoglucogenèse intestinale et des récepteurs mu-opioïdes dans les effets bénéfiques du by-pass gastrique chez la souris by Aude Barataud( )

1 edition published in 2014 in French and held by 1 WorldCat member library worldwide

Roux-en-Y gastric bypass procedure (GBP) is an obesity surgery that induces dramatic glucose homeostasis improvements independently of weight loss. A proposed mechanism to explain these glucose homeostasis improvements is an increase in intestinal glucose production (IGP) that induces beneficial effects on metabolism (satiety, improved liver insulin sensitivity). This increase in IGP is found in mice that have undergone a simplified GBP and is also responsible for the beneficial effects of protein-enriched diets through the inhibition of mu-opioid receptors (MOR) by alimentary peptides. We therefore hypothesized that the beneficial effects of GBP could depend on MOR inhibition by dietary proteins and we also tested the causal role of IGP in these metabolic improvements. For this purpose, we performed a duodenal-jejunal bypass surgery (DJB), ie GBP without gastric restriction, in wild-type mice (WT), in mice lacking MOR gene (MOR-/-) and in mice lacking IGP (IG6pc-/-). In obese mice, DJB induced a rapid and substantial weight loss (-30%), partly explained by fat malabsorption, and weight loss-dependent improvements of glucose homeostasis. In contrast, in the non-obese mice, DJB did not induce weight loss nor malabsorption but improved glucose tolerance. Effects were similar in WT, MOR-/- and I-G6pc-/- mice showing that mu-opioid receptors and IGP did not appear to have a causal role in glucose and energy metabolism improvements after DJB
Système endocannabinoïde et pathologies métaboliques chez l'Homme by Blandine Gatta-Chérifi( )

1 edition published in 2012 in French and held by 1 WorldCat member library worldwide

The endocannabinoid system (ECS) is a key system for the regulation of energy balance. Only few studies have been so far carried out in humans but they all lead to conclude that obese subjects have higher plasma fasting levels of the 2 major endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG). However, many questions concerning the role of the ECS in the physiopathology of obesity in humans remain still unanswered. This thesis has therefore attempted to address some of these questions by investigating i) the changes of plasma endocannabinoids in response to food intake, ii) the effect of weight loss induced by gastric bypass or lifestyle intervention on these plasma levels and iii) the potential link between insulin resistance and circulating endocannabinoids. Lastly, we have also tested the possibility to develop a non-invasive tool to ease the investigation of the ECS in humans. In the 1st study, we have described for the first time the existence of a pre-prandial peak in plasma AEA, which is independent of body weight. This evidence suggests that circulating AEA levels might work as a meal initiator factor in humans. Importantly, the AEA postprandial decrease is blunted in obese insulin resistant subjects and might therefore favor the persistence of the obese phenotype. In our 2nd study, preliminary results suggest that the same body weight loss obtained through gastric-bypass or lifestyle intervention differently affects plasma AEA levels. In particular, while AEA tend to increase in subjects who have undergone gastric bypass, no changes are observed after a comparable weight loss induced by lifestyle intervention. Thus, a possibility is that the bypass might directly affect the function of the ECS localized within the gastrointestinal tract. In our 3rd study, which was carried out on 8 type 2 diabetic patients, we have shown that 72 hours of a low carbohydrate diet significantly decreases glycaemia and insulin resistance, without affecting the levels and the kinetic of circulating endocannabinoids. Lastly, we demonstrated that endocannabinoids are reliably measured in saliva. Salivary endocannabinoids are higher in obese as compared to normal weight subjects. Body weight loss significantly decreases salivary AEA, while the consumption of a meal does not influence salivary endocannabinoids levels. Altogether our studies confirm the association between ECS deregulation and metabolic disease in humans. In particular, we have demonstrated that plasma AEA might have a physiological role in the regulation of human feeding behavior, and have hinted the potential relevance of the gastro-intestinal ECS in our studies on gastric-bypass patients. We have also shown that in type 2 diabetes, there is a flattening of the kinetics of circulating endocannabinoids. Finally, we have shown that measurement of salivary endocannabinoids is reliable and might be of clinical value. These findings extend our knowledge on one of the systems majorly implicated in energy balance regulation. Such knowledge is a necessary step towards the development of novel therapeutic strategies needed to halt obesity and metabolic disease
Role of pregnenolone derivative AEF0117 on the regulation of CB1 signaling that mediates behavioral effects of THC by Giovanni Tomaselli( )

1 edition published in 2020 in English and held by 1 WorldCat member library worldwide

Etude de l'intéraction entre les ros et la voie mtorc1 dans la régulation de la balance énergetique by Magali Haissaguerre( )

1 edition published in 2015 in French and held by 1 WorldCat member library worldwide

The mechanistic target of rapamycin complex 1 (mTORC1) pathway is an importanthypothalamic integrator of nutrients and hormones. Nutrient availability also affects thereactive oxygen species (ROS) in propiomelanocortin (POMC) neurons and regulatesneuronal activity. We hypothesize that modulation of mTORC1 activity mediates ROS effectson food intake.To this purpose, C57Bl6J mice or WT mice and their KO littermates either deficient for themTORC1 downstream target S6K1 or for the mTORC1 component raptor specifically inPOMC neurons (POMC-raptor-KO) were treated with an intracerebroventricular (ICV)injection of the ROS producer H2O2 or the ROS scavenger honokiol, alone or in combinationwith the mTOR inhibitor rapamycin or the mTOR activator leptin.ICV H2O2 induced phosphorylation of S6K1 within the hypothalamus, increased expressionof c-fos, a marker of neuronal activity, in the arcuate nucleus and increased ROS in POMCneurons. These effects were associated with a significant decrease in food intake. Theanorexigenic effect of ICV H2O2 was not seen in S6K1-KO mice, in C57Bl6J mice cotreatedwith rapamycin (an mTOR inhibitor) and in POMC-raptor-KO mice.Similarly, ICV honokiol administration combined with a leptin injection blunted theanorexigenic effect of leptin, suggesting that leptin requires ROS formation to reduce FI. ICVadministration of leptin increased ROS in POMC neurons in C57Bl6J and POMC-raptor-WTmice, but not in POMC-raptor-KO mice.Our results demonstrate that ROS modulators require a functional mTORC1 pathway toregulate food intake and that leptin needs an mTORC1-dependent increase in ROS levels inPOMC neurons to decrease food intake
Bile acids signaling as a novel mechanism in the hypothalamic control of energy balance. by Ashley Castellanos jankiewicz( )

1 edition published in 2019 in English and held by 1 WorldCat member library worldwide

Introduction : Les acides biliaires (AB) sont des molécules connues pour digérer les lipides. En activant le récepteur couplé à la protéine G Takeda 5 (TGR5) dans les tissus périphériques, ils peuvent également servir de molécules de signalisation pour réduire le poids corporel et améliorer le profil glycémique. L'activation de TGR5 peut aussi augmenter la dépense énergétique dans le tissu adipeux, mais les voies métaboliques impliquées dans ces effets sont encore mal connues. Ces observations impliquent une action anti-obésité du TGR5. Cependant, toutes les études sur les AB dans la balance énergétique se sont concentrées exclusivement sur des tissus périphériques. Comme le principal centre de convergence des signaux nutritifs, hormonaux et environnementaux se trouve dans le cerveau, et en particulier dans l'hypothalamus, nous avons émis l'hypothèse que l'activité hypothalamique du TGR5 pourrait moduler la balance énergétique, en particulier dans un contexte d'obésité. Objectif : Démontrer la fonction du système AB - TGR5 dans des populations de cellules hypothalamiques connues pour contrôler l'homéostasie énergétique et étudier sa pertinence pour le traitement de l'obésité. Méthodes : Des canules intra-cérébro-ventriculaires (ICV) ont été implantées sur des souris mâles C57Bl6/J minces (sous régime standard) ou obèses (sous régime riche en graisses) pour permettre l'administration pharmacologique aiguë ou chronique des agonistes du TGR5. Des souris TGR5flox/flox ont été utilisées pour provoquer la délétion du récepteur dans l'hypothalamus médio-basal (HMB), par l'injection in situ d'un AAV-Cre. Nous avons mesuré le poids corporel, prise alimentaire, composition corporelle, sensibilité à l'insuline, niveaux des AB hypothalamiques et plasmatiques et dépense énergétique. Pour bloquer la signalisation sympathique, nous avons exposé les souris à un environnement de thermoneutralité (30°C) ou à une sympathectomie chimique. Des marqueurs de la lipolyse, de la thermogenèse ou du métabolisme thyroïdien ont été mesurés dans le foie, le tissu adipeux et l'hypothalamus par qPCR ou western blot. Toutes les études ont été approuvées par le comité d'éthique en expérimentation animale de l'Université de Bordeaux. Résultats : Nous montrons que les transporteurs du TGR5 et des AB s'expriment dans l'HMB et que les souris obèses ont une diminution des AB dans la circulation et l'hypothalamus. L'administration aiguë d'agonistes du TGR5 (ICV ou intra-HMB) réduit la prise alimentaire et le poids corporel chez les souris obèses, tout en améliorant leur sensibilité à l'insuline. De plus, l'administration chronique ICV de l'agoniste réduit le poids corporel et l'adiposité, tout en augmentant la dépense énergétique et les marqueurs de l'activité sympathique dans le tissus adipeux. La thermo-neutralité ainsi que la sympathectomie chimique atténuent ces effets, démontrant que l'activité du récepteur TGR5 nécessite un tonus sympathique accru. La délétion de TGR5 dans le HMB (souris TGR5flox/flox) n'a aucun effet chez les souris minces. Cependant, l'exposition à une nourriture riche en graisse augmente rapidement leur poids, prise alimentaire et adiposité. Lors de l'exposition au froid (4 heures à 4°C), l'expression des marqueurs de lipolyse et thermogenèse dans le tissu adipeux était atténuée, suggérant une interruption de la signalisation sympathique. Enfin, la suppression du TGR5 dans le HMB de souris déjà obèses augmente l'adiposité en induisant une hyperphagie, aggravant l'obésité. Conclusions : Nos résultats prouvent l'existence d'un système fonctionnel du TGR5 hypothalamique, un récepteur des AB. Nous montrons pour la première fois que l'activation du TGR5 dans le HMB induit une myriade d'effets qui améliorent des paramètres métaboliques, et que cela dépend de l'activation du système nerveux sympathique. Ainsi, nous dévoilons un nouveau mécanisme d'action pour des potentiels traitements contre l'obésité
Characterization of different subpopulations of hypothalamic POMC neurons in the regulation of energy balance. by Vincent Simon( )

1 edition published in 2019 in English and held by 1 WorldCat member library worldwide

Obesity is a chronic multifactorial disease, characterized by a health-threatening accumulation of body fat and whose prevalence has been increasing worldwide since the 1980s. Obesity is a risk factor for type II diabetes, cardiovascular disease and various forms of cancer and is now a major public health issue. Unfortunately, available pharmacological treatments are rare and not very effective. Thus, the study of the biological mechanisms underlying body weight regulation could lead to the discovery of new therapeutic targets and prove useful in the fight against this modern curse. The brain plays a key role in controlling food intake and metabolism. In particular, some hypothalamic neurons called POMC neurons are classically described as being responsible for satiety. To date, most studies on these neurons have focused on their neuropeptide production, but recent discoveries have uncovered the existence of subpopulations, characterized by their ability to secrete different neurotransmitters (glutamate, GABA or both). The functional consequences of this heterogeneity are largely unknown to this day.The general objective of this thesis is to study the specific roles of different sub-populations of POMC neurons, depending on the neurotransmitter they release: we will then distinguish between POMC-Glut (pure glutamatergic), POMC-GABA (pure GABAergic) and POMC-Glut/GABA (mixed) neurons. Three objectives have been defined: To develop a new neuroanatomical technical approach to identify subpopulations of activated POMC neurons on mouse brain slices. To determine the impact of a hypercaloric diet on POMC subpopulations. To determine the role of the POMC Glutamatergic population in energy balance by using a novel genetic model. Results: First, we developed a new technique for the simultaneous detection of mRNAs of GAD65/67, vglut2 and POMC combined with an immunostaining of the cFos protein (a marker of cellular activity), in order to identify the subpopulations of activated POMC neurons under various experimental conditions. Then, we applied this technique in a context of an acute exposure to a high-calorie diet (HFD, for "high-fat-diet"). We then discovered that POMC-GABA neurons were the main sub-population to be activated by HFD, unlike POMC-Glut which were less likely to respond to the diet. Of note this preferential activation of POMC-GABA happens in a context of HFD-driven hyperphagia. Finally, we created a new genetically modified mouse line that allows the deletion of the vglut2 protein from POMC neurons in an inducible way, thus preventing the release of glutamate from POMC neurons. After carrying out the necessary controls, we conducted a metabolic characterization of this mouse line. Inducible POMC-vglut2-KO mice, in which POMC glutamatergic transmission is suppressed, have an exaggerated hyperphagic response following a 24-hour fast. In addition, when placed on a HFD, these mice eat more and have an increased energy expenditure. [...]
Role of intestinal gluconeogenesis on the neonatal development of hypothalamic feeding circuits by Judith Estrada Meza( )

1 edition published in 2020 in English and held by 1 WorldCat member library worldwide

Obesity increases the risk of developing diabetes and cardiovascular disease, and is a major public health challenge. Epidemiological, clinical and experimental data have highlighted the role of the perinatal environment on the development of metabolic diseases. The perinatal period is crucial for development and is therefore a very vulnerable period. Nutritional and hormonal insults arriving during the perinatal period can severely compromise the development of key organs that regulate energy balance, like the hypothalamus, and thus jeopardize life-long metabolic health. Hypothalamic AgRP/NPY (agouti-related peptide and neuropeptide Y) and POMC/CART (pro-opiomelanocortin and cocaine- and amphetamine-regulated transcript) feeding circuits develop during the first three weeks of life in rodents, under the influence of a postnatal surge of the hormone leptin. Leptin promotes axonal outgrowth from the arcuate nucleus by stimulating the STAT3 signaling pathway. A defective development of these axonal projections is associated with an adult onset of metabolic problems. Intestinal gluconeogenesis (IGN) exerts beneficial effects against obesity and diabetes in adults by targeting the STAT3 signaling pathway in POMC neurons from the arcuate nucleus. Interestingly, IGN doubles during the first two weeks of life in rodents. We therefore investigated whether neonatal IGN controls: 1) the development of AgRP/NPY and POMC/CART axonal projections from the arcuate nucleus; and 2) the susceptibility to develop obesity when exposed to a diet rich in fat and sugar (HFHS). Using a murine model with an intestine-specific, inducible overexpression of the catalytic subunit of the glucose-6-phosphatase, the mandatory enzyme for gluconeogenesis, we show that the induction of IGN since birth increases the density of arcuate nucleus AgRP axonal projections to the hypothalamic paraventricular nucleus. This effect is specific to the first two weeks of life because the induction of IGN on postnatal day 12 fails to affect AgRP fiber density. The neonatal induction of IGN before postnatal day 12 also protects adult mice from becoming obese when fed a HFHS diet. These data suggest that the neonatal peak of IGN exerts a neurotrophic effect on AgRP axons from the arcuate nucleus, and that inducing IGN during the first two weeks of life protects long-term adiposity
Le rôle respectif des différents populations de neurones épineux moyens du noyau accumbens dans la motivation et la prise alimentaire by Roman Walle( )

1 edition published in 2021 in French and held by 1 WorldCat member library worldwide

Les dérégulations de la prise alimentaire vue dans certaines formes d'obésités et anorexie nerveuse peuvent être considéré comme des pathologie opposée sur la base de leur symptomatologie, i.e. une augmentation/diminution de la prise alimentaire, diminution/augmentation de l'activité physique et la motivation dans l'obésité et AN, respectivement. Bien que les mécanismes physiopathologiques de ces pathologies restent encore obscure, plusieurs évidences suggèrent un dysfonctionnement du système mésolimbique et en particulier du noyaux accumbens (NAc). Mon projet de thèse vise à manipuler l'activité des différentes sous population neuronales du Nac et déterminer s'ils sont suffisant pour induire mimer les dimensions symptomatiques vue dans l'obésité et AN. Le Nac est principalement composé de neurones moyens épineux (MSN) qui sont ségrégés en 2 populations sur la base des récepteurs dopaminergiques qu'ils expriment, soit D1 (D1-MSN) ou D2 (D2-MSN). Par le biais d'une approche de pharmacogénétique associer à une analyse de la i) motivation ii) la prise alimentaire et iii) l'activité physique chez la souris, nous montrons que l'activation aigue des D2-MSNs ou D1-MSNs conduit respectivement à un phénotype associer à l'obésité et l'anorexie
 
moreShow More Titles
fewerShow Fewer Titles
Audience Level
0
Audience Level
1
  General Special  
Audience level: 0.95 (from 0.88 for Endocannab ... to 0.97 for Toward a n ...)

Alternative Names
Daniela Cota onderzoeker

Languages
English (10)

French (7)