المؤلفون: Reynaert, Marie-Line

مرشدي الرسالة: Lille 1, Maccari, Stefania, Morley-Fletcher, Sara

مصطلحات موضوعية: Stress prénatal, 571.938

الوصف: Le stress est un facteur d’importance dans l'étiologie des troubles de l'humeur et de l’addiction. Des rats stressés prénatalement (SPN), i.e. la progéniture de femelles soumises à des épisodes répétés de stress les 10 derniers jours de gestation, présentent des troubles liés au stress (anxiété, dépression, vulnérabilité aux drogues), avec un effet net du sexe dans le profil induit par le SPN : les mâles SPN sont anxieux alors que les rats SPN des 2 sexes présentent un comportement de type dépressif. Une diminution de la libération de glutamate dans l'hippocampe ventral est au cœur du profil d'anxiété des rats SPN et un traitement avec des antidépresseurs augmente la libération de glutamate et corrige le profil anxiodépressif. Ici, pour la 1ère fois, la modification des patterns circadiens, comme caractéristique de la dépression, a été analysée à la fois chez les rats mâles et femelles. Nous montrons une spécificité du genre pour l’effet du SPN sur les systèmes circadiens (activité locomotrice, resynchronisation pour un nouveau cycle lumière-obscurité, niveaux de CRH hypothalamique). Nous avons étendu l’étude de l'influence du sexe à l’addiction et démontré que 1)les hormones sexuelles jouent un rôle clé dans la réponse aux drogues dans un paradigme de préférence de place conditionnée; 2)la sensibilité est stimulus-dépendante (chocolat vs cocaïne). Enfin, nous montrons que l'augmentation de la préférence pour la cocaïne est liée à l'activation de la locomotion, mais aussi à l'effet anxiolytique/antidépresseur de la drogue, suggérant que la préférence pour une drogue augmente quand celle-ci est capable de corriger les troubles de l'humeur, renforçant l'hypothèse de l'automédication dans l’addiction.
Stress is an important factor in the etiology of mood disorders and addictive behaviors. Prenatally restraint stressed (PRS) rats, i.e. the offspring of dams submitted to repeated episodes of stress during the last ten days of gestation, display stress-related disorders (anxiety, depression, vulnerability to drugs of abuse), with a clear-cut sex effect in PRS-induced profile: PRS males are anxious while PRS rats of both sexes display a depressive-like behavior. An impairment of glutamate release in the ventral hippocampus lies at the core of the anxiety-like profile of PRS rats and we have shown that chronic treatment with antidepressants enhanced glutamate release and corrected PRS rats anxious-/depressive-like profile. Here, for the first time, the alteration of circadian patterns, as a feature of depression, was analyzed both in male and female rats. We have shown a gender-specific outcome of PRS on circadian patterns of locomotor activity, resynchronization to a new light-dark cycle, and hypothalamic CRH levels. We extended the impact of sex in our model to addiction and demonstrated that 1)sex hormones play a key role in determining rats preference for drugs in a conditioned place preference paradigm; 2)sensitiveness is stimulus-dependent (natural reward chocolate vs cocaine). Finally, we found that an enhanced preference for cocaine, shown in females and in PRS rats of both sexes, was linked to the locomotor activating effect of the drug but also to its anxiolytic and antidepressant effect. This suggests that preference for a drug is increased when the drug is able to correct mood disorders, reinforcing the hypothesis of self-medication in addiction.

الإتاحة: http://www.theses.fr/2014LIL10094/documentTest

المؤلفون: MORLEY-FLETCHER, Sara, Mairesse, Jerome, Van Camp, Gilles, Reynaert, Marie-Line, Gatta, Eleonora, Marrocco, Jordan, Bouwalerh, Hammou, Nicoletti, Ferdinando, Maccari, Stefania

المساهمون: Université de Lille, CNRS, Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576, University of Geneva Switzerland, Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 UGSF, University of Illinois Chicago UIC, Rockefeller University New York, Istituto Neurologico Mediterraneo NEUROMED I.R.C.C.S., Sapienza University Rome

مصطلحات موضوعية: predictive adaptation, reactive adaptation, circadian rhythms, locomotor activity, chronobiological stressor, mRNA expression

الوصف: Stress and the circadian systems play a major role in an organism’s adaptation to environmental changes. The adaptive value of the stress system is reactive while that of the circadian system is predictive. Dysfunctions in these two systems may account for many clinically relevant disorders. Despite the evidence that interindividual differences in stress sensitivity and in the functioning of the circadian system are related, there is limited integrated research on these topics. Moreover, sex differences in these systems are poorly investigated. We used the perinatal stress (PRS) rat model, a well-characterized model of maladaptive programming of reactive and predictive adaptation, to monitor the running wheel behavior in male and female adult PRS rats, under a normal light/dark cycle as well as in response to a chronobiological stressor (6-h phase advance/shift). We then analyzed across different time points the expression of genes involved in circadian clocks, stress response, signaling, and glucose metabolism regulation in the suprachiasmatic nucleus (SCN). In the unstressed control group, we found a sex-specific profile that was either enhanced or inverted by PRS. Also, PRS disrupted circadian wheel-running behavior by inducing a phase advance in the activity of males and hypoactivity in females and increased vulnerability to chronobiological stress in both sexes. We also observed oscillations of several genes in the SCN of the unstressed group in both sexes. PRS affected males to greater extent than females, with PRS males displaying a pattern similar to unstressed females. Altogether, our findings provide evidence for a specific profile of dysmasculinization induced by PRS at the behavioral and molecular level, thus advocating the necessity to include sex as a biological variable to study the set-up of circadian system in animal models. ; 12

وصف الملف: application/pdf; application/octet-stream

العلاقة: Frontiers in Molecular Neuroscience; Front. Mol. Neurosci.; http://hdl.handle.net/20.500.12210/34225.2Test

الإتاحة: https://doi.org/20.500.12210/34225.2Test
https://hdl.handle.net/20.500.12210/34225.2Test

المؤلفون: Zheng, Jin, Akbari, Mansour, Schirmer, Claire, Reynaert, Marie-Line, Loyens, Anne, Lefebvre, Bruno, Buée, Luc, Croteau, Deborah, Galas, Marie-Christine, Bohr, Vilhelm

المساهمون: University of Copenhagen = Københavns Universitet (UCPH), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille), National Institute on Aging Baltimore, MD, USA (NIH)

المصدر: ISSN: 2051-5960 ; Acta Neuropathologica Communications ; https://inserm.hal.science/inserm-02999922Test ; Acta Neuropathologica Communications, 2020, 8 (1), pp.25. ⟨10.1186/s40478-020-00896-8⟩.

مصطلحات موضوعية: Mitochondrial homeostasis, Oxidative stress, Polymerase beta, Tau oligomerization, Tauopathies, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]

الوصف: International audience ; Insoluble intracellular aggregation of tau proteins into filaments and neurodegeneration are histopathological hallmarks of Alzheimer disease (AD) and other tauopathies. Recently, prefibrillar, soluble, oligomeric tau intermediates have emerged as relevant pathological tau species; however, the molecular mechanisms of neuronal responses to tau oligomers are not fully understood. Here, we show that hippocampal neurons in six-month-old transgenic mouse model of tauopathy, THY-Tau22, are enriched with oligomeric tau, contain elongated mitochondria, and display cellular stress, but no overt cytotoxicity compared to the control mice. The levels of several key mitochondrial proteins were markedly different between the THY-Tau22 and control mice hippocampi including the mitochondrial SIRT3, PINK1, ANT1 and the fission protein DRP1. DNA base excision repair (BER) is the primary defense system against oxidative DNA damage and it was elevated in six-month-old transgenic mice. DNA polymerase β, the key BER DNA polymerase, was enriched in the cytoplasm of hippocampal neurons in six-month-old transgenic mice and localized with and within mitochondria. Polβ also co-localized with mitochondria in human AD brains in neurons containing oligomeric tau. Most of these altered mitochondrial and DNA repair events were specific to the transgenic mice at 6 months of age and were not different from control mice at 12 months of age when tau pathology reaches its maximum and oligomeric forms of tau are no longer detectable. In summary, our data suggests that we have identified key cellular stress responses at early stages of tau pathology to preserve neuronal integrity and to promote survival. To our knowledge, this work provides the first description of multiple stress responses involving mitochondrial homeostasis and BER early during the progression of tau pathology, and represents an important advance in the etiopathogenesis of tauopathies.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/32131898; inserm-02999922; https://inserm.hal.science/inserm-02999922Test; https://inserm.hal.science/inserm-02999922/documentTest; https://inserm.hal.science/inserm-02999922/file/s40478-020-00896-8.pdfTest; PUBMED: 32131898; PUBMEDCENTRAL: PMC7057491

الإتاحة: https://doi.org/10.1186/s40478-020-00896-8Test
https://inserm.hal.science/inserm-02999922Test
https://inserm.hal.science/inserm-02999922/documentTest
https://inserm.hal.science/inserm-02999922/file/s40478-020-00896-8.pdfTest

المؤلفون: Reynaert, Marie-Line, Dupoiron, Denis, Yeramian, Edouard, Marsollier, Laurent, C, Brodin, Priscille

المساهمون: Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Institut de Cancérologie de l'Ouest Angers/Nantes (UNICANCER/ICO), UNICANCER, Microbiologie structurale - Structural Microbiology (Microb. Struc. (UMR_3528 / U-Pasteur_5)), Institut Pasteur Paris (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), ATOMycA (CRCINA-ÉQUIPE 6), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Financial support for this work was provided by the region Pays de la Loire (Kalmos project), the Agence Nationale de Recherche (ANR-17-CE18-0001), the Institut Pasteur of Lille (granted to P.B. and M.L.R.), the Inserm Program ATIP avenir (granted to L.M), the region Pays de la Loire (Kalmos project) and Angers University., ANR-17-CE18-0001,AT2R-TRAAK-BIOANALGESICS,Caractérisations moléculaires et cellulaires de voies de signalisation de la douleur: contrôle de la douleur dans l'ulcère de buruli comme source d'inspiration pour la conception rationnelle de nouveaux analgésiques puissants(2017)

المصدر: EISSN: 2072-6651 ; Toxins ; https://inserm.hal.science/inserm-02284632Test ; Toxins, 2019, 11 (9), pp.516. ⟨10.3390/toxins11090516⟩

مصطلحات موضوعية: AT2R, drug development, neurons, analgesia, mycolactone, [SDV.CAN]Life Sciences [q-bio]/Cancer

الوصف: International audience ; Pain currently represents the most common symptom for which medical attention is sought by patients. The available treatments have limited effectiveness and significant side-effects. In addition, most often, the duration of analgesia is short. Today, the handling of pain remains a major challenge. One promising alternative for the discovery of novel potent analgesics is to take inspiration from Mother Nature; in this context, the detailed investigation of the intriguing analgesia implemented in Buruli ulcer, an infectious disease caused by the bacterium Mycobacterium ulcerans and characterized by painless ulcerative lesions, seems particularly promising. More precisely, in this disease, the painless skin ulcers are caused by mycolactone, a polyketide lactone exotoxin. In fact, mycolactone exerts a wide range of effects on the host, besides being responsible for analgesia, as it has been shown notably to modulate the immune response or to provoke apoptosis. Several cellular mechanisms and different targets have been proposed to account for the analgesic effect of the toxin, such as nerve degeneration, the inhibition of inflammatory mediators and the activation of angiotensin II receptor 2. In this review, we discuss the current knowledge in the field, highlighting possible controversies. We first discuss the different pain-mimicking experimental models that were used to study the effect of mycolactone. We then detail the different variants of mycolactone that were used in such models. Overall, based on the results and the discussions, we conclude that the development of mycolactone-derived molecules can represent very promising perspectives for new analgesic drugs, which could be effective for specific pain indications. Key Contribution: This review develops arguments and issues around the development of new potent analgesic drugs derived from mycolactone, a toxin secreted by Mycobacterium ulcerans. To this end, the various modes of action of the toxin potentially underlying its analgesic ...

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/31487908; inserm-02284632; https://inserm.hal.science/inserm-02284632Test; https://inserm.hal.science/inserm-02284632/documentTest; https://inserm.hal.science/inserm-02284632/file/Marsollier2019Eq6.pdfTest; PUBMED: 31487908

الإتاحة: https://doi.org/10.3390/toxins11090516Test
https://inserm.hal.science/inserm-02284632Test
https://inserm.hal.science/inserm-02284632/documentTest
https://inserm.hal.science/inserm-02284632/file/Marsollier2019Eq6.pdfTest

المؤلفون: Babonneau, Jérémie, Bréard, Dimitri, Reynaert, Marie-Line, Marion, Estelle, Guilet, David, Saint André, Jean-Paul, Croue, Anne, Brodin, Priscille, Richomme, Pascal, Marsollier, Laurent

المساهمون: ATOMycA (CRCINA-ÉQUIPE 6), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Substances d'Origine Naturelle et Analogues Structuraux (SONAS), Université d'Angers (UA), SFR UA 4207 QUAlité et SAnté du Végétal (QUASAV), Université d'Angers (UA)-Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-AGROCAMPUS OUEST-Ecole supérieure d'Agricultures d'Angers (ESA), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), CRLCC - Centre Paul Papin (CRLCC Paul Papin), Institut de Cancérologie de l'Ouest Angers/Nantes (UNICANCER/ICO), UNICANCER-UNICANCER, This work was supported by the region Pays de la Loire (Kalmos project), the Agence Nationale de Recherche (ANR-17-CE18-0001), the Institut Pasteur of Lille (granted to PB and M-LR), the Inserm Program ATIP avenir (granted to LM), the region Pays de la Loire (Kalmos project) and Angers University., ANR-17-CE18-0001,AT2R-TRAAK-BIOANALGESICS,Caractérisations moléculaires et cellulaires de voies de signalisation de la douleur: contrôle de la douleur dans l'ulcère de buruli comme source d'inspiration pour la conception rationnelle de nouveaux analgésiques puissants(2017)

المصدر: ISSN: 1663-9812 ; Frontiers in Pharmacology ; https://inserm.hal.science/inserm-02100552Test ; Frontiers in Pharmacology, 2019, 10, pp.378. ⟨10.3389/fphar.2019.00378⟩.

مصطلحات موضوعية: biological action, Mycobacterium ulcerans, mycolactone, analgesia, bioavailability, [SDV.CAN]Life Sciences [q-bio]/Cancer

الوصف: Jérémie Babonneau, Dimitri Bréard and Marie-Line Reynaert have contributed equally to this work. Priscille Brodin, Pascal Richomme and Laurent Marsollier are co-senior authors. ; International audience ; Mycobacterium ulcerans is the bacillus responsible for Buruli ulcer, an infectious disease and the third most important mycobacterial disease worldwide, after tuberculosis and leprosy. M. ulcerans infection is a type of panniculitis beginning mostly with a nodule or an oedema, which can progress to large ulcerative lesions. The lesions are caused by mycolactone, the polyketide toxin of M. ulcerans. Mycolactone plays a central role for host colonization as it has immunomodulatory and analgesic effects. On one hand, mycolactone induces analgesia by targeting type-2 angiotensin II receptors (AT 2 R), causing cellular hyperpolarization and neuron desensitization. Indeed, a single subcutaneous injection of mycolactone into the mouse footpad induces a long-lasting hypoesthesia up to 48 h. It was suggested that the long-lasting hypoesthesia may result from the persistence of a significant amount of mycolactone locally following its injection, which could be probably due to its slow elimination from tissues. To verify this hypothesis, we investigated the correlation between hypoesthesia and mycolactone bioavailability directly at the tissue level. Various quantities of mycolactone were then injected in mouse tissue and hypoesthesia was recorded with nociception assays over a period of 48 h. The hypoesthesia was maximal 6 h after the injection of 4 µg mycolactone. The basal state was reached 48 h after injection, which demonstrated the absence of nerve damage. Surprisingly, mycolactone levels decreased strongly during the first hours with a reduction of 70 and 90% after 4 and 10 h, respectively. Also, mycolactone did not diffuse in neighboring skin tissue and only poorly into the bloodstream upon direct injection. Nevertheless, the remaining amount was sufficient to induce hypoesthesia during 24 h. Our results thus ...

العلاقة: inserm-02100552; https://inserm.hal.science/inserm-02100552Test; https://inserm.hal.science/inserm-02100552/documentTest; https://inserm.hal.science/inserm-02100552/file/MarsollierEq6-2019.pdfTest

الإتاحة: https://doi.org/10.3389/fphar.2019.00378Test
https://inserm.hal.science/inserm-02100552Test
https://inserm.hal.science/inserm-02100552/documentTest
https://inserm.hal.science/inserm-02100552/file/MarsollierEq6-2019.pdfTest

المؤلفون: Morley-Fletcher, Sara, Mairesse, Jerome, van Camp, Gilles, Reynaert, Marie-Line, Gatta, Eleonora, Marrocco, Jordan, Bouwalerh, Hammou, Nicoletti, Ferdinando, Maccari, Stefania

المساهمون: Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université de Genève = University of Geneva (UNIGE), University of Illinois Chicago (UIC), University of Illinois System, Rockefeller University New York, Università degli Studi di Roma "La Sapienza" = Sapienza University Rome (UNIROMA), Istituto Neurologico Mediterraneo (NEUROMED I.R.C.C.S.), Università degli Studi di Roma "La Sapienza" = Sapienza University Rome (UNIROMA)-University of Naples Federico II = Università degli studi di Napoli Federico II

المصدر: ISSN: 1662-5099 ; Frontiers in Molecular Neuroscience ; https://hal.univ-lille.fr/hal-03094662Test ; Frontiers in Molecular Neuroscience, 2019, 12, ⟨10.3389/fnmol.2019.00089⟩.

مصطلحات موضوعية: predictive adaptation, reactive adaptation, circadian rhythms, locomotor activity, chronobiological stressor, mRNA expression, [SDV]Life Sciences [q-bio], [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry

الوصف: International audience ; Stress and the circadian systems play a major role in an organism’s adaptation to environmental changes. The adaptive value of the stress system is reactive while that of the circadian system is predictive. Dysfunctions in these two systems may account for many clinically relevant disorders. Despite the evidence that interindividual differences in stress sensitivity and in the functioning of the circadian system are related, there is limited integrated research on these topics. Moreover, sex differences in these systems are poorly investigated. We used the perinatal stress (PRS) rat model, a well-characterized model of maladaptive programming of reactive and predictive adaptation, to monitor the running wheel behavior in male and female adult PRS rats, under a normal light/dark cycle as well as in response to a chronobiological stressor (6-h phase advance/shift). We then analyzed across different time points the expression of genes involved in circadian clocks, stress response, signaling, and glucose metabolism regulation in the suprachiasmatic nucleus (SCN). In the unstressed control group, we found a sex-specific profile that was either enhanced or inverted by PRS. Also, PRS disrupted circadian wheel-running behavior by inducing a phase advance in the activity of males and hypoactivity in females and increased vulnerability to chronobiological stress in both sexes. We also observed oscillations of several genes in the SCN of the unstressed group in both sexes. PRS affected males to greater extent than females, with PRS males displaying a pattern similar to unstressed females. Altogether, our findings provide evidence for a specific profile of dysmasculinization induced by PRS at the behavioral and molecular level, thus advocating the necessity to include sex as a biological variable to study the set-up of circadian system in animal models.

العلاقة: hal-03094662; https://hal.univ-lille.fr/hal-03094662Test; https://hal.univ-lille.fr/hal-03094662/documentTest; https://hal.univ-lille.fr/hal-03094662/file/P19.87%20fnmol-12-00089%20%281%29.pdfTest

الإتاحة: https://doi.org/10.3389/fnmol.2019.00089Test
https://hal.univ-lille.fr/hal-03094662Test
https://hal.univ-lille.fr/hal-03094662/documentTest
https://hal.univ-lille.fr/hal-03094662/file/P19.87%20fnmol-12-00089%20%281%29.pdfTest

المؤلفون: Mairesse, Jérôme, Gatta, Eleonora, Reynaert, Marie-Line, Marrocco, Jordan, MORLEY-FLETCHER, Sara, Soichot, Marion, Deruyter, Lucie, Van Camp, Gilles, Bouwalerh, Hammou, Fagioli, Francesca, Pittaluga, Anna, Allorge, Delphine, Nicoletti, Ferdinando, Maccari, Stefania

المساهمون: CHU Lille, CNRS, Université de Lille, Institut Pasteur de Lille, IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - EA 4483, Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 UGSF, Rockefeller University New York, Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576, Faculté de Médecine Henri Warembourg - Université de Lille, Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 UGSF, Azienda Sanitaria Locale ROMA ASL, Università degli studi di Genova = University of Genoa UniGe, Istituto Neurologico Mediterraneo NEUROMED I.R.C.C.S.

مصطلحات موضوعية: Perinatal stress, Carbetocin, Anxiety, Social behavior, Glutamate, Ventral hippocampus

الوصف: Oxytocin receptors are known to modulate synaptic transmission and network activity in the hippocampus, but their precise function has been only partially elucidated. Here, we have found that activation of presynaptic oxytocin receptor with the potent agonist, carbetocin, enhanced depolarization-evoked glutamate release in the ventral hippocampus with no effect on GABA release. This evidence paved the way for examining the effect of carbetocin treatment in “prenatally restraint stressed” (PRS) rats, i.e., the offspring of dams exposed to repeated episodes of restraint stress during pregnancy. Adult PRS rats exhibit an anxious/depressive-like phenotype associated with an abnormal glucocorticoid feedback regulation of the hypothalamus-pituitary-adrenal (HPA) axis, and, remarkably, with a reduced depolarization-evoked glutamate release in the ventral hippocampus. Chronic systemic treatment with carbetocin (1 mg/kg, i.p., once a day for 2–3 weeks) in PRS rats corrected the defect in glutamate release, anxiety- and depressive-like behavior, and abnormalities in social behavior, in the HPA response to stress, and in the expression of stress-related genes in the hippocampus and amygdala. Of note, carbetocin treatment had no effect on these behavioral and neuroendocrine parameters in prenatally unstressed (control) rats, with the exception of a reduced expression of the oxytocin receptor gene in the amygdala. These findings disclose a novel function of oxytocin receptors in the hippocampus, and encourage the use of oxytocin receptor agonists in the treatment of stress-related psychiatric disorders in adult life. ; 62

وصف الملف: application/octet-stream

العلاقة: Psychoneuroendocrinology; http://hdl.handle.net/20.500.12210/18438Test

الإتاحة: https://doi.org/20.500.12210/18438Test
https://hdl.handle.net/20.500.12210/18438Test

المؤلفون: Maccari, Stefania, Polese, Daniela, Reynaert, Marie-Line, Amici, Tiziana, MORLEY-FLETCHER, Sara, Fagioli, Francesca

المساهمون: CNRS, Université de Lille, Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576, Università degli Studi di Roma "La Sapienza" Rome, Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 UGSF

مصطلحات موضوعية: epigenetics, animal models, annulment drive, vitality, Human Birth Theory, "anaffettività"

الوصف: In mammals, early adverse experiences, including mother–pup interactions, shape the response of an individual to chronic stress or to stress-related diseases during adult life. This has led to the elaboration of the theory of the developmental origins of health and disease, in particular adult diseases such as cardiovascular and metabolic disorders. In addition, in humans, as stated by Massimo Fagioli’s Human Birth Theory, birth is healthy and equal for all individuals, so that mental illness develop exclusively in the postnatal period because of the quality of the relationship in the first year of life. Thus, this review focuses on the importance of programming during the early developmental period on the manifestation of adult diseases in both animal models and humans. Considering the obvious differences between animals and humans we cannot systematically move from animal models to humans. Consequently, in the first part of this review, we will discuss how animal models can be used to dissect the influence of adverse events occurring during the prenatal and postnatal periods on the developmental trajectories of the offspring, and in the second part, we will discuss the role of postnatal critical periods on the development of mental diseases in humans. Epigenetic mechanisms that cause reversible modifications in gene expression, driving the development of a pathological phenotype in response to a negative early postnatal environment, may lie at the core of this programming, thereby providing potential new therapeutic targets. The concept of the Human Birth Theory leads to a comprehension of the mental illness as a pathology of the human relationship immediately after birth and during the first year of life. ; 342

وصف الملف: application/octet-stream

العلاقة: Neuroscience; http://hdl.handle.net/20.500.12210/18452.2Test

الإتاحة: https://doi.org/20.500.12210/18452.2Test
https://hdl.handle.net/20.500.12210/18452.2Test

المؤلفون: Reynaert, Marie-Line, Marrocco, Jordan, Mairesse, Jérôme, Lionetto, Luana, Simmaco, Maurizio, Deruyter, Lucie, Allorge, Delphine, Moles, Anna, Pittaluga, Anna, Maccari, Stefania, MORLEY-FLETCHER, Sara, Van Camp, Gilles, Nicoletti, Ferdinando

المساهمون: CHU Lille, CNRS, Université de Lille, Institut Pasteur de Lille, Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 UGSF, Istituto Neurologico Mediterraneo NEUROMED I.R.C.C.S., Centro Neurolesi Bonino Pulejo Messina IRCCS Messina, Azienda Ospedaliera Sant'Andrea Roma, 171461|||Impact de l'environnement chimique sur la santé humaine - ULR 4483 IMPECS, 235067, Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576, IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - EA 4483

مصطلحات موضوعية: Animal model, conditioned place preference, early life stress, palatable food, sex hormones

الوصف: Palatable food is a strong activator of the reward circuitry and may cause addictive behavior leading to eating disorders. How early life events and sex interact in shaping hedonic sensitivity to palatable food is largely unknown. We used prenatally restraint stressed (PRS) rats, which show abnormalities in the reward system and anxious/depressive-like behavior. Some of the hallmarks of PRS rats are known to be sex-dependent. We report that PRS enhanced and reduced milk chocolate-induced conditioned place preference in males and females, respectively. Male PRS rats also show increases in plasma dihydrotestosterone (DHT) levels and dopamine (DA) levels in the nucleus accumbens (NAc), and reductions in 5-hydroxytryptamine (5-HT) levels in the NAc and prefrontal cortex (PFC). In male rats, systemic treatment with the DHT-lowering drug finasteride reduced both milk chocolate preference and NAc DA levels. Female PRS rats showed lower plasma estradiol (E2) levels and lower DA levels in the NAc, and 5-HT levels in the NAc and PFC. E2 supplementation reversed the reduction in milk chocolate preference and PFC 5-HT levels. In the hypothalamus, PRS increased ERα and ERβ estrogen receptor and CARTP (cocaine-and-amphetamine receptor transcript peptide) mRNA levels in males, and 5-HT2C receptor mRNA levels in females. Changes were corrected by treatments with finasteride and E2, respectively. These new findings show that early life stress has a profound impact on hedonic sensitivity to high-palatable food via long-lasting changes in gonadal hormones. This paves the way to the development of hormonal strategies aimed at correcting abnormalities in the response to natural rewards. ; 21;6

وصف الملف: application/octet-stream

العلاقة: Addiction Biology; http://hdl.handle.net/20.500.12210/18436Test

الإتاحة: https://doi.org/20.500.12210/18436Test
https://hdl.handle.net/20.500.12210/18436Test

المؤلفون: Reynaert, Marie-Line, Hochart-Behra, Anne-Cécile, Behra-Miellet, Josette, Gressier, Bernard, Mine, Louis, Dine, Thierry, Luyckx, Michel, Dubreuil, Luc, Brunet, Claude

مصطلحات موضوعية: Original research

الوصف: Objectives The aim was to compare the in vitro effects of amoxicillin and ampicillin on the oxidative metabolism of polymorphonuclear neutrophils (PMNs). Methods Superoxide radical anion production by PMNs, stimulated or not by various exogenous stimulants and in contact with increasing antibiotic concentrations, was measured using spectrophotometric methods. Results Whereas a pro-oxidative action of amoxicillin on PMNs was obtained without exogenous stimulation or with opsonized zymosan (OZ), the O 2 − production by PMNs incubated with ampicillin did not increase significantly. Conclusions This amoxicillin pro-oxidative effect could be due to the activation of the PMN NADPH oxidase, to its induction by a membrane effect or via the OZ pathway. It probably reinforces amoxicillin intrinsic bactericidal action and might partly explain the severe rashes sometimes occurring with amoxicillin treatment.

وصف الملف: text/html

العلاقة: http://jac.oxfordjournals.org/cgi/content/short/dkn545v1Test; http://dx.doi.org/10.1093/jac/dkn545Test

الإتاحة: https://doi.org/10.1093/jac/dkn545Test
http://jac.oxfordjournals.org/cgi/content/short/dkn545v1Test