WorldCat Identities

Marsicano, Giovanni

Overview
Works: 26 works in 33 publications in 4 languages and 87 library holdings
Genres: Academic theses  History  Sources  Biographies  Bio-bibliography 
Roles: Author, Thesis advisor, Opponent, Other, Speaker
Publication Timeline
.
Most widely held works by Giovanni Marsicano
Cannabinoid type 1 receptors in astrocytes by Giovanni Marsicano( Visual )

3 editions published in 2014 in English and held by 48 WorldCat member libraries worldwide

Physiological role of the cannabinoid receptor 1 (CB1) in the murine central nervous system by Giovanni Marsicano( Book )

5 editions published between 2000 and 2001 in English and held by 6 WorldCat member libraries worldwide

<> by Haidong Wei( )

1 edition published in 2013 in English and held by 2 WorldCat member libraries worldwide

L'adolescence, une période de vulnérabilité aux effets de régimes obésogènes sur la mémoire : études des fonctions hippocampiques et amygdaliennes by Chloé Boitard( )

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

L'obésité, considérée comme pandémique, est associée à l'apparition de troubles cognitifs et émotionnels chez l'Homme comme chez l'animal. La prévalence de l'obésité augmente de manière drastique chez les enfants et les adolescents. Or l'adolescence est une période primordiale pour la maturation des structures cérébrales (notamment l'hippocampe et l'amygdale) qui vont sous-tendre les processus cognitifs pour le restant de la vie de l'individu. Cependant, aucune étude n'avait investigué la potentielle vulnérabilité de cette période développementale aux effets de l'obésité sur la mémoire, comparativement à l'âge adulte. Nous avons donc effectué cette comparaison chez le rongeur, en modélisant l'obésité par une exposition à un régime hyper-lipidique (HL) pendant une période incluant l'adolescence versus à l'âge adulte uniquement (i.e. excluant l'adolescence). Nous mettons en évidence que l'obésité induite à l'adolescence provoque des altérations mnésiques, qui ne sont pas retrouvés lorsque l'obésité est induite à l'âge adulte. La majorité des études sur les effets de l'obésité ayant mis en évidence une altération des mémoires dépendantes de l'hippocampe, nous nous sommes tout d'abord focalisés sur les fonctions hippocampiques. Nous avons ensuite exploré le système amygdalien, impliqué dans les mémoires émotionnelles et peu étudié dans le cadre de l'obésité. Ces deux systèmes fonctionnels ont été appréhendés au travers d'approches comportementales visant à évaluer les performances mnésiques, mais également d'approches d'imagerie cellulaire et d'électrophysiologie afin d'évaluer la plasticité cellulaire au sein de ces structures. Nous mettons en évidence que l'obésité induite à l'adolescence impacte la mémoire et la plasticité de ces systèmes de manière bidirectionnelle en dégradant les fonctions hippocampiques et en exacerbant les fonctions amygdaliennes. Concernant les mécanismes impliqués dans ces effets nous mettons en évidence l'existence d'une exacerbation de la réponse inflammatoire spécifiquement au niveau de l'hippocampe chez les animaux exposés au régime HL à l'adolescence, ce qui pourrait expliquer les déficits des fonctions hippocampiques. Enfin, nous montrons que la dérégulation de l'axe corticotrope chez ces animaux est responsable des effets comportementaux et cellulaires observés au niveau des fonctions amygdaliennes. L'ensemble de ces résultats montre l'urgence de développer les études sur l'obésité juvénile, dont les effets importants sur les fonctions cognitives et émotionnelles pourraient engendrer une altération importante de la qualité de vie et une prise en charge accrue de ces sujets tout au long de leur vie
Rôles des récepteurs cannabinoïdes de type 1 dans le cortex piriforme antérieur by Geoffrey Terral( )

1 edition published in 2018 in French and held by 1 WorldCat member library worldwide

Being involved in many behavioral functions, olfaction has powerful influence in guiding our actions. Odors communicate with the central nervous system via specialized receptors in the nose olfactory epithelium that generate neuronal signals, which in turn are eventually distributed and processed in many brain regions. In particular, the anterior piriform cortex (aPC) is an important olfactory area involved in perception and integration of odors. Given the extended role of the main cannabinoid type-1 (CB1) receptor in sensory and memory brain functions, we hypothesized that CB1 receptors could modulate odor processing in the aPC. To this aim, using a combination of anatomical, electrophysiological, and pharmacological approaches, we first characterized the distribution of CB1 receptors and their ability to regulate aPC circuits. We found that CB1 receptors are mainly expressed in GABAergic interneurons where their activation regulates inhibitory transmission and plasticity. Then, we evaluated the role and the impact of CB1 receptor modulation on odor-related aPC processing. In vivo calcium imaging revealed that odor-evoked aPC activity is affected by alteration of CB1 receptor signaling. Additionally, we demonstrated that physiological aPC-CB1 receptors functioning is necessary for retrieve appetitive but not aversive olfactory memory, likely through modulation of local inhibitory circuits. Overall, this work contribute to a better understanding of how CB1 receptors modulate olfactory processes in the aPC
The connectivity logic of cannabinoid type-1 expressing interneurones in the mouse visual cortex by Martin Montmerle( )

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

La perception sensorielle dépend d'une interaction constante entre plusieurs zones corticales. Typiquement, pour chaque sens il y a une zone primaire qui reçoit directement des informations sensorielles du thalamus et une zone secondaire qui associe cette information avec des centres cognitifs plus élaborés (information descendante). Pourtant, les propriétés synaptiques et les microcircuits impliqués dans ces différents processus ne sont toujours pas élucidés. Nous savons que le récepteur cannabinoïde de type 1 (CB1) est exprimé à un plus grand niveau dans les cortex sensoriels secondaires. Ce récepteur est principalement exprimé par des cellules paniers inhibitrices qui expriment aussi le peptide cholecystokinin (CCK). En utilisant des enregistrements entre des paires d'IN CCK/CB1 et NP dans la couche 2/3 (C2/3) des centres visuels primaires (V1) et secondaires (V2) de souris adultes, nous avons demontré que dans le V1 les IN CCK projettent quasiment exclusivement dans leur propre couche, tandis que dans le V2 ils projettent aussi dans la couche 4 (C4). Malgré cette difference morphologique, ces IN avaient les mêmes signatures électrophysiologiques, suggérant qu'il s'agisse bien d'un type cellulaire homogène. En revanche, les connections synaptiques avec les NP étaient nettement plus petites et non fiable dans la C2/3 de V2. Cette différence disparut avec l'application d'un antagoniste de CB1, suggérant que ce récepteur médie une inhibition tonique qui est spécifique à une zone et couche corticale. Cette étude montre ainsi qu'il existe des microcircuits inhibiteurs particuliers dans les aires primaires et secondaires visuelles
Etude du rôle de VGLUT3, un transporteur vésiculaire du glutamate atypique, dans l'amygdale cérébrale dans le contexte de peur acquise by Nida Chabbah( )

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

Post-Traumatic Stress Disorder (PTSD) is an anxiety-like disorder usually triggered by a traumatic experience. Brain structures such as the prefrontal cortex, the hippocampus or the amygdala belonging to the learning and emotional memories network, are particularly affected. As this network is extremely well conserved during evolution, acquisition and consolidation of aversive memories can be studied by a Pavlovian fear conditioning paradigm in rodents. Our team has identified a strong expression of the vesicular glutamate transporter, VGLUT3 in the basolateral amygdala (BLA). VGLUT3 allows, like all vesicular transporters, neurotransmitter internalization, here the glutamate in synaptic vesicles. VGLUT3 is atypical because of its distribution and its functions. The aim of my work is to identify the neuronal population expressing VGLUT3 in the amygdala as well as its role in processing aversive memories. The anatomical characterisation revealed: 1/ VGLUT3 mRNA in BLA GABAergic interneurons, 2/ VGLUT3 protein in cholinergic and serotoninergic terminals in the BLA, identifying two populations of projecting neurons expressing VGLUT3. To decipher the functional role of VGLUT3, we used viral and genetic approaches to ablate VGLUT3 either in GABAergic, serotoninergic or cholinergic terminals. Mice lacking VGLUT3 constitutively show contextual generalization and rapid extinction. Specific inactivation of VGLUT3 in BLA impairs aversive memories, shedding light on a specific role of VGLUT3 in modulating fear responses through its presence in BLA interneurons. These new data will be discussed in the context of PTSD and would open a new direction for the development of therapeutic treatment
Plasticité morphofonctionnelle du système de l'immunité innée cérébrale : modulation par l'inflammation et la nutrition by Charlotte Madore( )

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

The brain innate immune system is mainly composed of microglial cells. Microglia are activated in response to an immune or inflammatory stimuli or a trauma, and then produce pro- and anti-inflammatory factors. These factors drive the innate immune response and can modulate neuronal activity and in fine, learning and memory. Recently, microglia have been shown to play a key role during brain development. Via their phagocytic activity, microglial cells can participate to neuronal networks maturation. Although brain innate immune system defends brain tissue from aggression, chronic activation of microglia can also be deleterious. In the adult brain, chronic production of inflammatory cytokines can contribute to the pathogenesis of neurodegenerative diseases. During development, inflammatory stimuli modifying microglia activity and homeostasis could lead to neuropsychiatric diseases with a neurodevelopmental origin. Understanding how microglia are regulated and how they respond to various stimuli is therefore crucial.Microglia activity is characterized by morphological and dynamic properties of microglia,by its communication with neurons by its polarization into a specific phenotype, and by their phagocytic profile. Few studies have characterized all the morphofunctional properties of microglial cells in vivo. Using a combination of approaches including FACS, immunohistochemistry, confocal microscopy, 3D reconstruction, two-photon microscopy and communication factors assays, it is now possible to better characterize these cells in order to understand their regulation by the environment and the resulting impact (beneficial or deleterious) on neuronal functions. The main goal of this thesis was to study the morphofunctional properties of microglial cells in vivo in two pathophysiological states: a peripheral inflammation induced by a peripheral injection of lipopolysaccharide (LPS) and in an n-3 PUFAs nutritional state. In the first study, we developed tools to investigate microglial morphofunctional plasticity and gained a better understanding of the impact of peripheral inflammation on the activity of these cells in vivo. In the second part of this thesis, we showed for the first time that maternal nutritional status in n-3 PUFAs affect the morphofunctional properties of microglial cells and the establishment of neural circuits during the postnatal development of the pups. Overall, our results provide new insights in the relationship between morphological and functional plasticity of microglial cells in vivo
Opposite control of frontocortical 2-arachidonoylglycerol turnover rate by cannabinoid type-1 receptors located on glutamatergic neurons and on astrocytes( )

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

Abstract This study examined the respective influences of cannabinoid type-1 (CB1) receptors expressed either in forebrain GABAergic neurons, in cortical glutamatergic neurons, or in astrocytes on the turnover rates of the endocannabinoids N-arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG), and the non-cannabinoid N-acylethanolamides, palmitoylethanolamide (PEA), and oleoylethanolamide (OEA), in mouse forebrain regions. To this end, conditional mutant mice lacking CB1 receptors from either of these cell types were pre-treated systemically with JZL195, a dual inhibitor of fatty acid amide hydrolase, the enzyme degrading AEA, PEA, and OEA, and of monoacylglycerol lipase, the main 2-AG-degrading enzyme. The analyses of frontocortical, hippocampal, and striatal AEA, 2-AG, PEA, and OEA concentrations revealed that their respective baseline concentrations were not influenced by the mouse genotype. On the other hand, the accumulation of frontocortical and/or hippocampal 2-AG levels in JZL195-pre-treated mice was dependent on the mouse genotype. Thus, JZL195-induced 2-AG accumulation rates were diminished in the frontal cortex of mice lacking CB1 receptors in glutamatergic neurons while their respective values were increased in the frontal cortex and hippocampus of mice lacking these receptors in astrocytes. These genotypic differences occurred with parallel and proportionate changes in the fractional rate constants for degradation of 2-AG, thus providing a mechanism whereby the baseline levels of 2-AG remained constant between genotypes. Besides suggesting a cell-type-specific control of frontocortical and/or hippocampal 2-AG synthesis and degradation rates by CB1 receptors, this study highlights the interest of assessing endocannabinoid turnover rates when questioning the status of the endocannabinoid system. In mice lacking CB1 receptors from glutamatergic neurons (Glu-CB1−/−) or from astrocytes (GFAP-CB1−/−), frontocortical and hippocampal 2-AG levels are not altered. Turnover studies indicate, however, that decreased 2-AG synthesis occurs with decreased degradation in Glu-CB1−/− mice, whereas the opposite is observed in GFAP-CB1−/− mice. 2-AG, 2-arachidonoylglycerol; CB1, cannabinoid type-1; Glu, glutamate
Cell-type specific CB1 receptor modulation of hippocampal synaptic plasticity and memory by Jose Fernando Oliveira Da Cruz( )

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

The endocannabinoid system is a major brain modulatory system that controls memory and learning mainly via the cannabinoid receptor type 1 (CB1)-dependent regulation of neuronal and glial activity. In the hippocampus, bidirectional communication between neurons and astrocytes shapes synaptic plasticity and behavior. CB1 receptors have been shown to be present in the astrocytes and to mediate the disruptive effects of cannabinoids in synaptic plasticity and working memory. Yet, it is not currently known the role of this receptor in the physiological modulation of memory processes. Also, previous studies have shown that CB1 receptors expressed in dopamine D1 receptor-expressing cells are involved in the modulation of hippocampal-dependent aversive memories. However, their involvement in the modulation of non-aversive long-term memory formation and synaptic plasticity is presently unknown. In this thesis, I aimed at identifying the cellular and molecular mechanisms by which specific CB1 receptors in distinct brain neuronal and glial populations contribute to the physiological modulation of synaptic plasticity and learning and memory. For this aim we used conditional genetic mutant mice lacking CB1 receptors specifically in astrocytes or in D1-positive cells. By coupling these genetic mouse models with behavioral, pharmacological, and in vitro and in vivo electrophysiological approaches, we dissected the role of these CB1 receptors in the formation of memory. First, we show that astroglial CB1 receptors in the hippocampus control long-term potentiation (LTP) of CA3-CA1 synaptic transmission and long-term recognition memory. By allowing physiological availability of D-serine at NMDA receptors via gliotransmission, astrocytes are important elements controlling glia-neuron interactions that underlie synaptic plasticity and memory functions. The data show that astroglial CB1 receptors control plasticity and memory by regulating the synaptic availability of D-serine at NMDA receptors. Second, we show that CB1 receptors D1-positive cells control the consolidation, but not acquisition, of new memories and the enhancement of LTP induced by learning, showing that specific subpopulations CB1 receptor-expressing cells differentially modulate these processes.Overall, by showing that the endocannabinoid system in astrocytes is an important modulator of learning and memory and by suggesting that CB1 receptors in D1-positive cells are important for specific components of memory formation, we provide functional evidence for the complex cell type-dependent regulation of long-term recognition memory by the CB1 receptors
Anatomical Characterization of the Type-1 cannabinoid receptors in specific brain cell populations of mutant mice by Ana Gutierrez Rodriguez( )

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

The Cannabinoid Type I receptor protein (CB1) expression in the hippocampus of rescue mice modified to express the gene exclusively in specific brain cell types: such as dorsal telencephalic glutamatergic neurons, or GABAergic neurons have been analyzed. Furthermore, aiming at knowing the exact anatomical distribution of the astroglial CB1 receptors with respect to the excitatory and inhibitory synapses, the CB1 receptor expression in astrocytes of mouse expressing CB1 receptor only in astrocytes and mutant mouse expressing the protein hrGFP into astrocytes (that allows for better detection of the astrocytic processes) have been also investigated. The results showed that the majority of the hippocampal synapses surrounded by CB1 receptor immunopositive astrocytes in the 400-800 nm range are of excitatory nature. Moreover, the CB1 receptor rescue mutant mice characterized in this Doctoral Thesis have proven 1) to express CB1 receptors in specific brain cell types; 2) the re-expression is limited to the particular brain cell populations; 3) the endogenous levels of CB1 receptors are maintained in the brain cell types re-expressing the receptor. Which makes this mutant mice excellent tools for functional and translational investigations on the role of the CB1 receptors in the normal and diseased brain
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 du récepteur cannabinoïde de type 1 sur des populations neuronales spécifiques dans la régulation de l'équilibre énergétique by Luigi Bellocchio( )

1 edition published in 2010 in French and held by 1 WorldCat member library worldwide

Le système endocannabinoïde (SEC) a récemment émergé comme un important modulateurde la prise alimentaire et de la balance énergétique. Les récepteurs cannabinoïdes de type 1(récepteurs CB1) et ses ligands endogènes, le 2-arachidonoyl-glycérol (2-AG) et l'anandamide(AEA), sont largement présents au sein du cerveau ainsi qu'au niveau des organespériphériques impliqués dans la régulation du métabolisme énergétique, tels que le foie, letissu adipeux, les muscles squelettiques, le pancréas et le tractus gastro-intestinal. Lastimulation pharmacologique des récepteurs CB1 conduit généralement à une augmentation dela prise et du stockage énergétique, tandis que les antagonistes CB1 exercent les effets opposéschez l'animal ainsi que chez l'homme. De surcroît, des corrélations ont été établies entre unesur régulation pathologique du SEC et les troubles métaboliques.Pourtant, plusieurs preuves indiquent que la relation entre le SEC et le métabolismeénergétique pourrait être plus complexe, probablement à cause de la multiplicité des sites oùle SEC peut agir à travers l'organisme. L'objectif général de ce travail de thèse fut dedisséquer les différents mécanismes par lesquels le SEC régule la prise alimentaire etl'équilibre énergétique. Le premier Chapitre de cette thèse détaille les mécanismes neuronauxmodulant l'équilibre énergétique chez les mammifères. Dans le Chapitre II, nous analysonsles différents types neuronaux cérébraux responsables de l'impact de la signalisation desrécepteurs CB1 sur la prise alimentaire stimulée. Dans le Chapitre III, nous proposons que leblocage pharmacologique des récepteurs CB1 exerce un effet anorexigène en agissant sur lesneurones périphériques sympathiques. Enfin, au cours du Chapitre IV nous disséquons le rôlepossible des récepteurs CB1 sur la balance énergétique.Les antagonistes CB1 ont été montrés comme n'exerçant que des effets anorexigènestransitoires, ceux-ci disparaissant après quelques semaines de traitement chez l'animal etquelques mois chez des patients obèses. De plus, les agonistes CB1 résultent en des effets biphasiques typiques. En effet, des doses faibles à modérées augmentent la prise alimentairechez l'animal tandis que de fortes doses diminuent les comportements d'ingestion. Lesrécepteurs CB1 sont exprimés sur différentes populations neuronales, dont les neuronesGABAergiques et glutamatergiques corticaux. Puisque l'activation des récepteurs CB1 induitgénéralement une réduction de la libération des neurotransmetteurs, il est probable que leseffets manifestement contradictoires des manipulations pharmacologiques soient dus à cetteexpression différentielle des récepteurs CB1. En combinant les approches pharmacologiqueset génétiques, nous avons montré que les récepteurs CB1 localisés au niveau du striatumventral sont associés à une action hypophagique via une inhibition de la transmissionGABAergique. Au contraire, les récepteurs CB1 cérébraux modulant les transmissionsexcitatrices sous-tendent l'effet orexigène bien connu des cannabinoïdes (Chapitre II).L'injection aiguë de l'antagoniste CB1, le SR141716 (Rimonabant) a un puissant effetanorexigène dans des conditions de prise alimentaire stimulée, telles que l'hyperphagieinduite par le jeûne. Néanmoins, la nature de cet effet (centrale versus périphérique) ainsi queles circuits neuronaux impliqués sont encore objets d'investigations. Dans le Chapitre III,nous mettons en évidence que l'hypophagie induite par le Rimonabant est indépendante d'unemodulation des transmissions GABAergique, glutamatergique corticale ou sérotoninergiquepar les récepteurs CB1 dans le cerveau, aussi bien que d'actions intrinsèques des récepteursCB1 au niveau de différents noyaux hypothalamiques. En fait, le Rimonabant inhibe la prisealimentaire stimulée en potentialisant directement l'activité du système périphériquesympathique.En ce qui concerne les fonctions métaboliques du SEC, il n'est actuellement pas encoreclairement établi si ce sont les récepteurs CB1 exprimés sur les neurones ou ceux localisés surles organes métaboliques périphériques qui jouent un rôle majeur dans le contrôle du stockageet de la consommation énergétique dans des conditions physiologiques ou pathologiques.Dans ce scenario, au Chapitre IV, nous montrons que les récepteurs CB1 neuronaux jouent unrôle clé dans le développement de l'obésité induite par la diète. Les souris mutantesconditionnelles caractérisées par une délétion des récepteurs CB1 au niveau des neurones duprosencéphale et des neurones périphériques sympathiques (connus pour contrôler la prisealimentaire et le poids corporel) mais pas au niveau des organes périphériques, exhibent unphénotype de type mince ainsi qu'une résistance à l'obésité induite par la diète. Ce phénotyperésulte d'une augmentation de l'oxydation des lipides et de la thermogenèse associée à unediminution de l'absorption énergétique due à une potentialisation de l'activité sympathique.Dans le Chapitre V, nous discutons de la signalisation neuronale des récepteurs CB1 commeune clé déterminante de l'action du SEC sur l'équilibre énergétique. Nous proposons que lesrécepteurs CB1 exercent un contrôle bimodal sur le comportement alimentaire et régulent lesdépenses énergétiques ainsi que l'activité du système nerveux sympathique. Les différencesentre le rôle des agonistes endogènes versus exogènes des récepteurs CB1, mais aussi entre lesagonistes versus antagonistes suggèrent que ces récepteurs pourraient bénéficier de propriétéspharmacologiques particulières à la signalisation du type cellulaire impliqué
Droghe endogene by Giovanni MARSICANO( )

1 edition published in 2010 in Italian and held by 1 WorldCat member library worldwide

Cell Type-Specific Control of Memory Functions by CB1 Cannabinoid Receptors by Mathilde Metna-Laurent( )

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

Rôle de la sérine astrocytaire dans l'apprentissage et la mémoire et ses implications dans la maladie d'Alzheimer. by Marianne Maugard( )

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

Memory loss is among the first symptoms reported by patients suffering from Alzheimer's disease (AD). AD is characterized by extracellular amyloid plaques and intracellular aggregations of tau. A decrease of brain glucose metabolism has also been described in the brain of AD patients. Since this decrease appears decades before memory loss, we hypothesize that metabolic deficits could directly contribute to AD physiopathology. To understand the mechanisms linking brain metabolism and synaptic activity, we proposed to study the production of L-serine, a signaling molecule whose de novo synthesis diverts part of the glycolytic flux. L-serine is the precursor of D-serine, a co-agonist of N-methyl-D-aspartate receptors (NMDA-R) that is required to maintain long term potentiation (LTP) of synaptic activity in the hippocampus. Since both L- and D-serine are formed through the activity of the Phosphorylated Pathway that diverts part of the glycolytic flux, any metabolic deficits may impact synaptic activity.We developed a model of conditional Phgdh deletion, the first enzyme of the phosphorylated pathway, by stereotaxically injecting Adeno-Associated Vectors allowing the expression of Cre recombinase in the hippocampus of Phgdh(flox/flox) mice, a mice strain with loxP sites flanking exons 4 and 5 of Phgdh gene. We validated this model showing that Phgdh expression and D-serine level are decreased by 60% in the hippocampus of injected mice. We performed electrophysiological recordings and showed that LTP is significantly reduced in mice injected with Cre recombinase. Those mice also show long term memory deficits in the Morris Water Maze test. Those deficits are restored by chronically feeding Cre injected mice with a diet enriched in L-serine indicating that serine biosynthesis is necessary and sufficient for synaptic plasticity and long term memory.To assess whether this pathway may be involved in AD pathogenesis, we quantified the expression of several enzymes of the serine biosynthesis pathway in human brain samples and found major changes in AD patients even at intermediate stages. To further investigate this hypothesis, we used 3xTg-AD mice, a mouse model for AD showing deficits in brain metabolism, synaptic activity and cognition. LTP deficits in 3xTg mice are restored by acute supplementation of L- or D-serine on hippocampal slices. We show that chronic administration of D-serine restores long term spatial memory. It suggests that serine biosynthesis is an important pathway in AD
Impact de la consommation précoce d'un régime hyperlipidique obésogène sur différents systèmes de mémoire by Yootana Janthakhin( )

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

Clinical and experimental studies have established that obesity, resulting mainly from consumption of energy-dense food such as high-fat diet (HFD), is associated with adverse cognitive and emotional outcomes. The prevalence of obesity during childhood and adolescence has reached epidemic levels. This is particularly worrisome since these periods are crucial for hippocampal and amygdala maturation, two brain structures necessary for shaping memory and emotional functions. It is thus critical to determine the impact of HFD exposure during these early developmental periods on memory and emotional processes. First, we show that perinatal HFD exposure (throughout gestation and lactation), leads to dendritic shrinkage of pyramidal neurons in the CA1 of the hippocampus but also in the basolateral amygdala (BLA) in adult rats. These results add to the growing literature indicating changes in hippocampal-dependent memory after perinatal HFD exposure. Regarding amygdala, perinatal HFD exposure specifically impairs odor aversion memory, a task highly dependent on BLA function, without affecting olfactory or malaise processing. These results are the first to show that perinatal HFD exposure impairs amygdala functions, at cellular and behavioral levels. Next, we investigated the cellular mechanisms underlying memory impairment induced by adolescent HFD consumption. We first show that HFD consumption from weaning to adulthood (covering adolescence) impairs long-term, but not short-term, object recognition memory (ORM) in novel context condition which was associated with higher circulating corticosterone and enhanced hippocampal endocannabinoid levels (anandamide in particular) in HFD-fed mice. Systemic post-training blockade of glucocorticoid receptors (GR) or cannabinoid receptors type 1 (CB1R) prevented HFD-induced memory deficits. These treatments also normalized training-induced c-Fos over-activation specifically in hippocampus in HFD group stressing the importance of this structure. Indeed, hippocampal CB1R deletion improved memory in HFD-fed mice. Moreover, we identified changes of in vivo hippocampal synaptic plasticity after training as a potential mechanism impaired by HFD in a CB1R-dependent manner. Finally, chemogenetic inhibition of hippocampal glutamatergic cells improved memory in HFD group similarly to CB1R deletion or blockade suggesting CB1R-dependent disinhibition of these neurons in HFD-fed mice. These results indicate that high-fat diet consumption during adolescence alters the hippocampal eCB system leading to impairment of hippocampal synaptic plasticity and deficit in recognition memory consolidation. Taken together, our results provide new evidences of how HFD consumption during early developmental periods exerts its deleterious effects on cognitive functions and identify the endocannabinoid system as a potential target for treating cognitive impairment associated with obesity
Le rôle du récepteur des cannabinoïde de type 1 dans la consommation d'eau by Zhe Zhao( )

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

Water intake is crucial for maintaining body fluid homeostasis and animals' survival. Complex brain processes trigger thirst, which arises upon losing blood volume (i.e. extracellular dehydration) or increasing blood osmolality (i.e. intracellular dehydration), to replenish water for fluid balance. The brain plays a key role in modulating these processes, but the central mechanisms regulating water intake are not fully understood. Type-1 cannabinoid receptors (CB1) are widely and abundantly expressed in the central nervous system where they modulate a variety of functions, such as memory, anxiety and feeding behavior. However, the role of CB1 receptors in the control of water intake is still a matter of debate, since pharmacological activation or blockade of CB1 receptors produced contradictory results in drinking behavior experiments.My thesis work focuses on the role of CB1 receptors in the control of water intake. By using genetic, pharmacological, anatomical, imaging, and behavioral approaches, I examined the involvement of CB1 receptors in the control of water intake induced by different physiological conditions of extracellular or intracellular dehydration. The results showed that CB1 receptor signaling is required to promote water intake. In particular, global deletion of CB1 receptors does not change plasma osmolality and body water composition, but it decreases water intake induced by water deprivation, systemic or intracerebroventricular (ICV) administration of sodium chloride, or ICV injection of the peptide hormone angiotensin II. In the attempt to better detail the neuronal mechanisms of this function, I discovered that the presence of CB1 receptors in cortical glutamatergic neurons, particularly the ones located in the anterior cingulate cortex (ACC) glutamatergic neurons promote drinking behavior. CB1 receptors are abundantly expressed in axon terminal of ACC glutamatergic neurons projecting to the basolateral amygdala (BLA) and selective expression of CB1 receptors in this circuit is sufficient to guarantee proper drinking behavior in mice. Altogether, these data reveal that CB1 receptors are necessary to promote water intake, and that their presence in the ACC-BLA circuit is sufficient for the top-down control of drinking behavior.Furthermore, I also provided evidence that CB1 controls water intake in different conditions at other levels, e.g. insular cortex, cholinergic cells, and mitochondria.In summary, my thesis work analyzed the role of CB1 receptors in distinct cell populations/neuronal circuits for the control of water intake. These results will help further understanding the functions of the ECS and the brain regulation of thirst
La dipendenza dalle droghe by Pier-Vincenzo PIAZZA( )

1 edition published in 2010 in Italian and held by 1 WorldCat member library worldwide

 
moreShow More Titles
fewerShow Fewer Titles
Audience Level
0
Audience Level
1
  General Special  
Audience level: 0.72 (from 0.59 for Cannabinoi ... to 1.00 for Cannabinoi ...)

Alternative Names
Giovanni Marsicano researcher

Giovanni Marsicano wetenschapper

Languages
English (17)

French (6)

Latin (2)

Italian (2)