101 results on '"Comai, Stefano"'
Search Results
2. Dysfunction in endocannabinoids, palmitoylethanolamide, and degradation of tryptophan into kynurenine in individuals with depressive symptoms
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Comai, Stefano, Nunez, Nicolas, Atkin, Tobias, Ghabrash, Maykel F., Zakarian, Rita, Fielding, Allan, Saint-Laurent, Marie, Low, Nancy, Sauber, Garrett, Ragazzi, Eugenio, Hillard, Cecilia J., and Gobbi, Gabriella
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- 2024
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3. Neuroinflammation and kynurenines in schizophrenia: Impact on cognition depending on cognitive functioning and modulatory properties in relation to cognitive remediation and aerobic exercise
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Sapienza, Jacopo, Agostoni, Giulia, Comai, Stefano, Nasini, Sofia, Dall'Acqua, Stefano, Sut, Stefania, Spangaro, Marco, Martini, Francesca, Bechi, Margherita, Buonocore, Mariachiara, Bigai, Giorgia, Repaci, Federica, Nocera, Daniela, Ave, Chiara, Guglielmino, Carmelo, Cocchi, Federica, Cavallaro, Roberto, Deste, Giacomo, and Bosia, Marta
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- 2024
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4. Substantially elevated serum glutamate and CSF GOT-1 levels associated with cerebral ischemia and poor neurological outcomes in subarachnoid hemorrhage patients
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Snider, Silvia, Albano, Luigi, Gagliardi, Filippo, Comai, Stefano, Roncelli, Francesca, De Domenico, Pierfrancesco, Pompeo, Edoardo, Panni, Pietro, Bens, Nicole, Calvi, Maria Rosa, Mortini, Pietro, and Ruban, Angela
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- 2023
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5. Melatonin MT1 receptors as a target for the psychopharmacology of bipolar disorder: A translational study
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Tassan Mazzocco, Margherita, Pisanu, Claudia, Russo, Luigi, Acconcia, Clementina, Cambiaghi, Marco, De Girolamo, Sofia, Squassina, Alessio, Cherchi, Laura, Monzani, Elena, Scebba, Francesca, Angeloni, Debora, De Gregorio, Danilo, Nasini, Sofia, Dall’Acqua, Stefano, Sut, Stefania, Suprani, Federico, Garzilli, Mario, Guiso, Beatrice, Pulcinelli, Vittoria, Iaselli, Maria Novella, Pinna, Ilaria, Somaini, Giulia, Arru, Laura, Corrias, Carolina, Paribello, Pasquale, Pinna, Federica, Gobbi, Gabriella, Valtorta, Flavia, Carpiniello, Bernardo, Manchia, Mirko, and Comai, Stefano
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- 2023
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6. Repeated lysergic acid diethylamide (LSD) reverses stress-induced anxiety-like behavior, cortical synaptogenesis deficits and serotonergic neurotransmission decline
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De Gregorio, Danilo, Inserra, Antonio, Enns, Justine P., Markopoulos, Athanasios, Pileggi, Michael, El Rahimy, Youssef, Lopez-Canul, Martha, Comai, Stefano, and Gobbi, Gabriella
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- 2022
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7. Lysergic acid diethylamide (LSD) promotes social behavior through mTORC1 in the excitatory neurotransmission
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De Gregorio, Danilo, Popic, Jelena, Enns, Justine P., Inserra, Antonio, Skalecka, Agnieszka, Markopoulos, Athanasios, Posa, Luca, Lopez-Canul, Martha, Qianzi, He, Lafferty, Christopher K., Britt, Jonathan P., Comai, Stefano, Aguilar-Valles, Argel, Sonenberg, Nahum, and Gobbi, Gabriella
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- 2021
8. Selective Enhancement of REM Sleep in Male Rats through Activation of Melatonin MT1 Receptors Located in the Locus Ceruleus Norepinephrine Neurons.
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López-Canul, Martha, Qianzi He, Sasson, Tania, Ettaoussi, Mohamed, De Gregorio, Danilo, Ochoa-Sanchez, Rafael, Catoire, Helene, Posa, Luca, Rouleau, Guy, Beaulieu, Jean Martin, Comai, Stefano, and Gobbi, Gabriella
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RAPID eye movement sleep ,NON-REM sleep ,NORADRENALINE ,NEURONS ,RATS ,MELATONIN - Abstract
Sleep disorders affect millions of people around the world and have a high comorbidity with psychiatric disorders. While current hypnotics mostly increase non-rapid eye movement sleep (NREMS), drugs acting selectively on enhancing rapid eye movement sleep (REMS) are lacking. This polysomnographic study in male rats showed that the first-in-class selective melatonin MT
1 receptor partial agonist UCM871 increases the duration of REMS without affecting that of NREMS. The REMS-promoting effects of UCM871 occurred by inhibiting, in a dose–response manner, the firing activity of the locus ceruleus (LC) norepinephrine (NE) neurons, which express MT1 receptors. The increase of REMS duration and the inhibition of LC-NE neuronal activity by UCM871 were abolished by MT1 pharmacological antagonism and by an adeno-associated viral (AAV) vector, which selectively knocked down MT1 receptors in the LC-NE neurons. In conclusion, MT1 receptor agonism inhibits LC-NE neurons and triggers REMS, thus representing a novel mechanism and target for REMS disorders and/or psychiatric disorders associated with REMS impairments. [ABSTRACT FROM AUTHOR]- Published
- 2024
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9. Investigating the relationship between melatonin levels, melatonin system, microbiota composition and bipolar disorder psychopathology across the different phases of the disease
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Manchia, Mirko, Squassina, Alessio, Pisanu, Claudia, Congiu, Donatella, Garzilli, Mario, Guiso, Beatrice, Suprani, Federico, Paribello, Pasquale, Pulcinelli, Vittoria, Iaselli, Maria Novella, Pinna, Federica, Valtorta, Flavia, Carpiniello, Bernardo, and Comai, Stefano
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- 2019
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10. Age-related effects of exogenous melatonin on anxiety-like behavior in C57/B6J mice
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Nasini, Sofia, Tidei, Sara, Shkodra, Atea, De Gregorio, Danilo, Cambiaghi, Marco, and Comai, Stefano
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sociability ,mice ,melatonin ,anxiety ,adolescents ,adults ,local field potentials ,hippocampus ,medial prefrontal cortex ,aging - Published
- 2023
11. The novel uncompetitive NMDA receptor antagonist esmethadone (REL-1017) has no meaningful abuse potential in recreational drug users.
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Shram, Megan J., Henningfield, Jack E., Apseloff, Glen, Gorodetzky, Charles W., De Martin, Sara, Vocci, Frank L., Sapienza, Frank L., Kosten, Thomas R., Huston, Jeff, Buchhalter, August, Ashworth, Judy, Lanier, Ryan, Folli, Franco, Mattarei, Andrea, Guidetti, Clotilde, Comai, Stefano, O'Gorman, Cedric, Traversa, Sergio, Inturrisi, Charles E., and Manfredi, Paolo L.
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- 2023
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12. Psychopathological and sociodemographic features in treatment-resistant unipolar depression versus bipolar depression: a comparative study
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Nuñez, Nicolas A., Comai, Stefano, Dumitrescu, Eduard, Ghabrash, Maykel F., Tabaka, John, Saint-Laurent, Marie, Vida, Stephen, Kolivakis, Theodore, Fielding, Allan, Low, Nancy, Cervantes, Pablo, Booij, Linda, and Gobbi, Gabriella
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- 2018
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13. Effects of repeated lysergic acid diethylamide (LSD) on the mouse brain endocannabinoidome and gut microbiome.
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Inserra, Antonio, Giorgini, Giada, Lacroix, Sebastien, Bertazzo, Antonella, Choo, Jocelyn, Markopolous, Athanasios, Grant, Emily, Abolghasemi, Armita, De Gregorio, Danilo, Flamand, Nicolas, Rogers, Geraint, Comai, Stefano, Silvestri, Cristoforo, Gobbi, Gabriella, and Di Marzo, Vincenzo
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LSD (Drug) ,ERGOT alkaloids ,GUT microbiome ,LIQUID chromatography-mass spectrometry ,NEURAL transmission ,RIBOSOMAL DNA - Abstract
Background and Purpose: Psychedelics elicit prosocial, antidepressant and anxiolytic effects via neuroplasticity, neurotransmission and neuro‐immunomodulatory mechanisms. Whether psychedelics affect the brain endocannabinoid system and its extended version, the endocannabinoidome (eCBome) or the gut microbiome, remains unknown. Experimental Approach: Adult C57BL/6N male mice were administered lysergic acid diethylamide (LSD) or saline for 7 days. Sociability was assessed in the direct social interaction and three chambers tests. Prefrontal cortex and hippocampal endocannabinoids, endocannabinoid‐like mediators and metabolites were quantified via high‐pressure liquid chromatography with tandem mass spectrometry (HPLC‐MS/MS). Neurotransmitter levels were assessed via HPLC‐UV/fluorescence. Gut microbiome changes were investigated by 16S ribosomal DNA sequencing. Key Results: LSD increased social preference and novelty and decreased hippocampal levels of the N‐acylethanolamines N‐linoleoylethanolamine (LEA), anandamide (N‐arachidonoylethanolamine) and N‐docosahexaenoylethanolamine (DHEA); the monoacylglycerol 1/2‐docosahexaenoylglycerol (1/2‐DHG); the prostaglandins D2 (PGD2) and F2α (PGF2α); thromboxane 2 and kynurenine. Prefrontal eCBome mediator and metabolite levels were less affected by the treatment. LSD decreased Shannon alpha diversity of the gut microbiota, prevented the decrease in the Firmicutes:Bacteroidetes ratio observed in saline‐treated mice and altered the relative abundance of the bacterial taxa Bifidobacterium, Ileibacterium, Dubosiella and Rikenellaceae RC9. Conclusions and Implications: The prosocial effects elicited by repeated LSD administration are accompanied by alterations of hippocampal eCBome and kynurenine levels, and the composition of the gut microbiota. Modulation of the hippocampal eCBome and kynurenine pathway might represent a mechanism by which psychedelic compounds elicit prosocial effects and affect the gut microbiome. [ABSTRACT FROM AUTHOR]
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- 2023
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14. Biological Factors Underpinning Suicidal Behaviour: An Update.
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Abou Chahla, Maya N., Khalil, Mahmoud I., Comai, Stefano, Brundin, Lena, Erhardt, Sophie, and Guillemin, Gilles J.
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YOUNG adults ,CAUSES of death ,MENTAL illness ,SUICIDE ,ATTEMPTED suicide - Abstract
Suicide, a global health burden, represents the 17th leading cause of death worldwide (1.3%), but the 4th among young people aged between 15 and 29 years of age, according to World Health Organization (WHO), 2019. Suicidal behaviour is a complex, multi-factorial, polygenic and independent mental health problem caused by a combination of alterations and dysfunctions of several biological pathways and disruption of normal mechanisms in brain regions that remain poorly understood and need further investigation to be deciphered. Suicide complexity and unpredictability gained international interest as a field of research. Several studies have been conducted at the neuropathological, inflammatory, genetic, and molecular levels to uncover the triggers behind suicidal behaviour and develop convenient and effective therapeutic or at least preventive procedures. This review aims to summarise and focus on current knowledge of diverse biological pathways involved in the neurobiology of suicidal behaviour, and briefly highlights future potential therapeutic pathways to prevent or even treat this significant public health problem. [ABSTRACT FROM AUTHOR]
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- 2023
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15. CCNP Award Paper: Unveiling the role of melatonin [MT.sub.2] receptors in sleep, anxiety and other neuropsychiatric diseases: a novel target in psychopharmacology
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Comai, Stefano and Gobbi, Gabriella
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Melatonin -- Dosage and administration ,Psychopharmacology -- Research ,Anxiety -- Physiological aspects -- Health aspects ,Sleep -- Physiological aspects -- Health aspects ,Health ,Psychology and mental health - Abstract
Background: Melatonin (MLT) is a pleiotropic neurohormone controlling many physiological processes and whose dysfunction may contribute to several different diseases, such as neurodegenerative diseases, circadian and mood disorders, insomnia, type 2 diabetes and pain. Melatonin is synthesized by the pineal gland during the night and acts through 2 G-protein coupled receptors (GPCRs), [MT.sub.1](MEL1a) and [MT.sub.2] (MEL1b). Although a bulk of research has examined the physiopathological effects of MLT, few studies have investigated the selective role played by [MT.sub.1] and [MT.sub.2] receptors. Here we have reviewed current knowledge about the implications of [MT.sub.2] receptors in brain functions. Methods: We searched PubMed, Web of Science, Scopus, Google Scholar and articles reference lists for studies on [MT.sub.2] receptor ligands in sleep, anxiety, neuropsychiatric diseases and psychopharmacology, including genetic studies on the MTNR1B gene, which encodes the melatonin [MT.sub.2] receptor. Results: These studies demonstrate that [MT.sub.2] receptors are involved in the pathophysiology and pharmacology of sleep disorders, anxiety, depression, Alzheimer disease and pain and that selective [MT.sub.2] receptor agonists show hypnotic and anxiolytic properties. Limitations: Studies examining the role of [MT.sub.2] receptors in psychopharmacology are still limited. Conclusion: The development of novel selective [MT.sub.2] receptor ligands, together with further preclinical in vivo studies, may clarify the role of this receptor in brain function and psychopharmacology. The superfamily of GPCRs has proven to be among the most successful drug targets and, consequently, [MT.sub.2] receptors have great potential for pioneer drug discovery in the treatment of mental diseases for which limited therapeutic targets are currently available., Introduction Melatonin (MLT) is a neurohormone synthesized from serotonin (5-HT) and secreted foremost by the mammalian pineal gland following a distinct circadian rhythm with the acrophase during the dark phase [...]
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- 2014
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16. Sex Differences in Responses to Antidepressant Augmentations in Treatment-Resistant Depression.
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Moderie, Christophe, Nuñez, Nicolas, Fielding, Allan, Comai, Stefano, and Gobbi, Gabriella
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MENTAL depression ,HAMILTON Depression Inventory ,ANTIDEPRESSANTS ,MOOD stabilizers ,DEPRESSION in men ,DULOXETINE - Abstract
Background Women are nearly twice as likely as men to suffer from major depressive disorder. Yet, there is a dearth of studies comparing the clinical outcomes of women and men with treatment-resistant depression (TRD) treated with similar augmentation strategies. We aimed to evaluate the effects of the augmentation strategies in women and men at the McGill University Health Center. Methods We reviewed health records of 76 patients (42 women, 34 men) with TRD, treated with augmentation strategies including antidepressants (AD) with mood stabilizers (AD+MS), antipsychotics (AD+AP), or in combination (AD+AP+MS). Clinical outcomes were determined by comparing changes on the 17-item Hamilton Depression Rating Scale (HAMD-17), Montgomery-Åsberg Depression Rating Scale (MADRS), Quick Inventory of Depressive Symptomatology (QIDS-C16), and Clinical Global Impression rating scale (CGI-S) at the beginning and after 3 months of an unchanged treatment. Changes in individual items of the HAMD-17 were also compared between the groups. Results Women and men improved from beginning to 3 months on all scales (P < .001, η
p 2 ≥ 0.68). There was also a significant sex × time interaction for all scales (P < .05, ηp 2 ≥ 0.06), reflecting a greater improvement in women compared with men. Specifically, women exhibited greater improvement in early (P = .03, ηp 2 = 0.08) and middle-of-the-night insomnia (P = .01, ηp 2 = 0.09) as well as psychomotor retardation (P < .001 ηp 2 = 0.16) and psychic (P = .02, ηp 2 = 0.07) and somatic anxiety (P = .01, ηp 2 = 0.10). Conclusions The combination of AD+AP/MS generates a significantly greater clinical response in women compared with men with TRD, supporting the existence of distinct pharmacological profiles between sexes in our sample. Moreover, they emphasize the benefit of augmentation strategies in women, underscoring the benefit of addressing symptoms such as insomnia and anxiety with AP and MS. [ABSTRACT FROM AUTHOR]- Published
- 2022
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17. Novel selective melatonin MT2 receptor agonist in the treatment of insomnia
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Gobbi G., Ochoa Sanchez R., COMAI , STEFANO, Gobbi, G., Comai, Stefano, and Ochoa Sanchez, R.
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- 2014
18. Distinct role of melatonin MT1 and MT2 receptors in sleep and anxiety: insights from melatonin receptor knockout mice
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COMAI , STEFANO, Ochoa Sanchez R., Gobbi G., Comai, Stefano, Ochoa Sanchez, R., and Gobbi, G.
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- 2014
19. D-Lysergic Acid Diethylamide (LSD) as a Model of Psychosis: Mechanism of Action and Pharmacology.
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De Gregorio, Danilo, Comai, Stefano, Posa, Luca, and Gobbi, Gabriella
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LSD (Drug) ,PSYCHOSES ,SEROTONIN ,DOPAMINE ,HALLUCINOGENIC plants - Abstract
D-Lysergic Acid Diethylamide (LSD) is known for its hallucinogenic properties and psychotic-like symptoms, especially at high doses. It is indeed used as a pharmacological model of psychosis in preclinical research. The goal of this review was to understand the mechanism of action of psychotic-like effects of LSD. We searched Pubmed, Web of Science, Scopus, Google Scholar and articles' reference lists for preclinical studies regarding the mechanism of action involved in the psychotic-like effects induced by LSD. LSD's mechanism of action is pleiotropic, primarily mediated by the serotonergic system in the Dorsal Raphe, binding the 5-HT
2A receptor as a partial agonist and 5-HT1A as an agonist. LSD also modulates the Ventral Tegmental Area, at higher doses, by stimulating dopamine D2 , Trace Amine Associate receptor 1 (TAAR1 ) and 5-HT2A . More studies clarifying the mechanism of action of the psychotic-like symptoms or psychosis induced by LSD in humans are needed. LSD's effects are mediated by a pleiotropic mechanism involving serotonergic, dopaminergic, and glutamatergic neurotransmission. Thus, the LSD-induced psychosis is a useful model to test the therapeutic efficacy of potential novel antipsychotic drugs, particularly drugs with dual serotonergic and dopaminergic (DA) mechanism or acting on TAAR1 receptors. [ABSTRACT FROM AUTHOR]- Published
- 2016
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20. Hypnotic and Anxiolytic Properties of the Selective Melatonin MT2 Receptor Partial Agonist UCM765
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Comai, Stefano, Ochoa-Sanchez, Rafael, Rainer, Quentin, Gabriella Gobbi, Comai, Stefano, Ochoa Sanchez, Rafael, Rainer, Quentin, and Gobbi, Gabriella
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- 2013
21. Differential Function of Melatonin MT1 and MT2 Receptors in REM and NREM Sleep.
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Gobbi, Gabriella and Comai, Stefano
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SLEEP ,MELATONIN ,RAPID eye movement sleep ,NON-REM sleep ,SLEEP disorders - Abstract
The pathophysiological function of the G-protein coupled melatonin MT
1 and MT2 receptors has not yet been well-clarified. Recent advancements using selective MT1 / MT2 receptor ligands and MT1 /MT2 receptor knockout mice have suggested that the activation of the MT1 receptors are mainly implicated in the regulation of rapid eye movement (REM) sleep, whereas the MT2 receptors selectively increase non-REM (NREM) sleep. Studies in mutant mice show that MT1 knockout mice have an increase in NREM sleep and a decrease in REM sleep, while MT2 knockout mice a decrease in NREM sleep. The localization of MT1 receptors is also distinct from MT2 receptors; for example, MT2 receptors are located in the reticular thalamus (NREM area), while the MT1 receptors in the Locus Coeruleus and lateral hypothalamus (REM areas). Altogether, these findings suggest that these two receptors not only have a very specialized function in sleep, but that they may also modulate opposing effects. These data also suggest that mixed MT1 -MT2 receptors ligands are not clinically recommended given their opposite roles in physiological functions, confirmed by the modest effects of melatonin or MT1 /MT2 non-selective agonists when used in both preclinical and clinical studies as hypnotic drugs. In sum, MT1 and MT2 receptors have specific roles in the modulation of sleep, and consequently, selective ligands with agonist, antagonist, or partial agonist properties could have therapeutic potential for sleep; while the MT2 agonists or partial agonists might be indicated for NREM-related sleep and/or anxiety disorders, the MT1 agonists or partial agonists might be so for REM-related sleep disorders. Furthermore, MT1 but not MT2 receptors seem involved in the regulation of the circadian rhythm. Future research will help further develop MT1 and/or MT2 receptors as targets for neuropsychopharmacology drug development. [ABSTRACT FROM AUTHOR]- Published
- 2019
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22. NEUROCYTOKYNES CHANGES INDUCING PEG-INTERFERON-ALPHA DEPRESSION: A RATIONAL APPROACH TO INCREASE ADHERENCE OF THERAPY IN CHRONIC HEPATITIS C
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CAVALLETTO L, A. BERTAZZO, FERRI G, BERNARDINELLO E, AMODIO P, STERRONTINO D, PERINI GI, GATTA A, CHEMELLO L., COMAI , STEFANO, Cavalletto, L, A., Bertazzo, Ferri, G, Bernardinello, E, Comai, Stefano, Amodio, P, Sterrontino, D, Perini, Gi, Gatta, A, and Chemello, L.
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- 2008
23. A Tryptophan metabolism via serotonin in human CSF of different brain sites using a new neuroendoscopic technique
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Longatti, Pierluigi, Comai, Stefano, Perin, A., Bertazzo, Antonella, Rizzo, V., Ragazzi, Eugenio, Costa, C. V. L., Allegri, G., P., Longatti, Comai, Stefano, A., Perin, A., Bertazzo, V., Rizzo, E., Ragazzi, C. V. L., Costa, and G., Allegri
- Abstract
A new neuroendoscopy technique has permitted a precise and accurate exploration of all the cerebral ventricles, making possible the study of CSF of the lateral ventricles and, above all, the CSF adjacent to the walls of the third ventricle in man. The concentrations of tryptophan and its metabolites via serotonin were measured in CSF of different sites of the cerebral cavity, in particular in the third ventricle. Patients affected with non-communicating hydrocephalus undergoing neuroendoscopic third ventriculostomy were enrolled in the study. As controls, subjects not suffering from any neurological disease, who underwent lumbar subarachnoid anaesthesia for minor surgical procedures, provided lumbar CSF, and patients affected by Chiari malformation provided cisternal and right ventricular CSF. Tryptophan concentration was higher in right ventricular CSF than in lumbar CSF. Serotonin (5-HT) was detectable in the CSF of the right ventricle of hydrocephalic individuals. 5-Hydroxyindoleacetic acid (5-HIAA) was higher in the right ventricular CSF than in cisternal and lumbar CSF both in controls and hydrocephalic subjects. However, 5-HIAA level was higher in right ventricular and cisternal CSF in hydrocephalic individuals in comparison to controls. 5-HT presented the highest concentration in pineal recess, whereas the highest amounts of 5-HIAA were found in the choroids plexus, third and right ventricles and the lowest in the pineal recess, subarachnoid space and intepeduncular cistern melatonin is more concentrated within the ventricles, in particular the third ventricle, and in the CSF pineal recess. The use of this neuroendoscopic technique in hydrocephalic patients provides new insight on the metabolic pathway of tryptophan via serotonin in the CSF.
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- 2007
24. Tryptophan metabolism via serotonin in human CSF on different brain sites using a new neuroendoscopic technique
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P. LONGATTI, A. PERIN, A. BERTAZZO, V. RIZZO, C. V. L. COSTA, G. ALLEGRI, COMAI , STEFANO, P., Longatti, Comai, Stefano, A., Perin, A., Bertazzo, V., Rizzo, C. V. L., Costa, and G., Allegri
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- 2006
25. Production of indirubin and indigoids in humans
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Allegri G, Bertazzo A, Costa C.V.L., COMAI , STEFANO, Meijer L, Guyard N, Skaltsounis L, Eisenbrand G, Allegri, G, Bertazzo, A, Comai, Stefano, and Costa, C. V. L.
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- 2006
26. An investigation based on MALDI/MS on the possibile role of tryptophan and 7-hydroxytryptophan in melanogenesis
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A. BERTAZZO, A. SMANIOTTO, C. V. L. COSTA, G. ALLEGRI, P. TRALDI, COMAI , STEFANO, A., Bertazzo, A., Smaniotto, Comai, Stefano, C. V. L., Costa, G., Allegri, and P., Traldi
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- 2006
27. Melatonin: a possible substrate in the mechanism of melanogenesis
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BERTAZZO A., RIZZI A., COSTA C. V. L., ALLEGRI G., COMAI , STEFANO, Bertazzo, A., Comai, Stefano, Rizzi, A., Costa, C. V. L., and Allegri, G.
- Published
- 2005
28. Role of 7-hydroxytryptophan, a new potent chemiotherapeutic agent, in the biosynthesis of melanins. Comparison with 5-hydroxytryptophan
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COMAI , STEFANO, BERTAZZO A., SMANIOTTO A, COSTA C. V. L., ALLEGRI G., Comai, Stefano, Bertazzo, A., Smaniotto, A, Costa, C. V. L., and Allegri, G.
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- 2005
29. Possible role of melatonin in melanogenesis
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RIZZI A., BERTAZZO A., COSTA C. V. L., ALLEGRI G., TRALDI P., COMAI , STEFANO, Rizzi, A., Comai, Stefano, Bertazzo, A., Costa, C. V. L., Allegri, G., and Traldi, P.
- Published
- 2005
30. Transcranial direct current stimulation of the mouse prefrontal cortex modulates serotonergic neural activity of the dorsal raphe nucleus.
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Cambiaghi, Marco, Buffelli, Mario, Masin, Laura, Valtorta, Flavia, and Comai, Stefano
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- 2020
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31. An investigation on the role of 3-hydroxykynurenine in pigment formation by MALDI-MS
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S. VOGLIARDI, A. BERTAZZO, C. V. L. COSTA, ALLEGRI G., R. SERAGLIA, P. TRALDI, COMAI , STEFANO, S., Vogliardi, A., Bertazzo, Comai, Stefano, C. V. L., Costa, Allegri, G., R., Seraglia, and P., Traldi
- Published
- 2004
32. Translational control of depression-like behavior via phosphorylation of eukaryotic translation initiation factor 4E.
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Aguilar-Valles, Argel, Haji, Nabila, De Gregorio, Danilo, Matta-Camacho, Edna, Eslamizade, Mohammad J., Popic, Jelena, Sharma, Vijendra, Cao, Ruifeng, Rummel, Christoph, Tanti, Arnaud, Wiebe, Shane, Nuñez, Nicolas, Comai, Stefano, Nadon, Robert, Luheshi, Giamal, Mechawar, Naguib, Turecki, Gustavo, Lacaille, Jean-Claude, Gobbi, Gabriella, and Sonenberg, Nahum
- Abstract
Translation of mRNA into protein has a fundamental role in neurodevelopment, plasticity, and memory formation; however, its contribution in the pathophysiology of depressive disorders is not fully understood. We investigated the involvement of MNK1/2 (MAPK-interacting serine/threonine-protein kinase 1 and 2) and their target, eIF4E (eukaryotic initiation factor 4E), in depression-like behavior in mice. Mice carrying a mutation in eIF4E for the MNK1/2 phosphorylation site (Ser209Ala, Eif4e ki/ki), the Mnk1/2 double knockout mice (Mnk1/2 −/−), or mice treated with the MNK1/2 inhibitor, cercosporamide, displayed anxiety- and depression-like behaviors, impaired serotonin-induced excitatory synaptic activity in the prefrontal cortex, and diminished firing of the dorsal raphe neurons. In Eif4e ki/ki mice, brain IκBα, was decreased, while the NF-κB target, TNFα was elevated. TNFα inhibition in Eif4e ki/ki mice rescued, whereas TNFα administration to wild-type mice mimicked the depression-like behaviors and 5-HT synaptic deficits. We conclude that eIF4E phosphorylation modulates depression-like behavior through regulation of inflammatory responses. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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33. Effects of quetiapine and olanzapine in patients with psychosis and violent behavior: a pilot randomized, open-label, comparative study.
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Gobbi, Gabriella, Comai, Stefano, and Debonnel, Guy
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QUETIAPINE , *OLANZAPINE , *ANTIPSYCHOTIC agents , *AGGRESSION (Psychology) , *PSYCHODIAGNOSTICS - Abstract
Objective: Patients suffering from psychosis are more likely than the general population to commit aggressive acts, but the therapeutics of aggressive behavior are still a matter of debate. Methods: This pilot randomized, open-label study compared the efficacy of quetiapine versus olanzapine in reducing impulsive and aggressive behaviors (primary endpoints) and psychotic symptoms (secondary endpoints) from baseline to days 1, 7, 14, 28, 42, 56, and 70, in 15 violent schizophrenic patients hospitalized in a maximum-security psychiatric hospital. Results: Quetiapine (525±45 mg) and olanzapine (18.5±4.8 mg) were both efficacious in reducing Impulsivity Rating Scale from baseline to day 70. In addition, both treatments reduced the Brief Psychiatric Rating Scale, Positive and Negative Syndrome Scale, and Clinical Global Impression Scale scores at day 70 compared to baseline, and no differences were observed between treatments. Moreover, quetiapine, but not olanzapine, yielded an improvement of depressive symptoms in the items "depression" in Brief Psychiatric Rating Scale and "blunted affect" in Positive and Negative Syndrome Scale. Modified Overt Aggression Scale scores were also decreased from baseline to the endpoint, but due to the limited number of patients, it was not possible to detect a significant difference. Conclusion: In this pilot study, quetiapine and olanzapine equally decreased impulsive and psychotic symptoms after 8 weeks of treatment. Double-blind, large studies are needed to confirm the validity of these two treatments in highly aggressive and violent schizophrenic patients. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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34. Unveiling the role of melatonin MT2 receptors in sleep, anxiety and other neuropsychiatric diseases: a novel target in psychopharmacology.
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Comai, Stefano and Gobbi, Gabriella
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ANXIETY , *CELL receptors , *MELATONIN , *MENTAL illness , *SLEEP , *DRUG development - Abstract
Background: Melatonin (MLT) is a pleiotropic neurohormone controlling many physiological processes and whose dysfunction may contribute to several different diseases, such as neurodegenerative diseases, circadian and mood disorders, insomnia, type 2 diabetes and pain. Melatonin is synthesized by the pineal gland during the night and acts through 2 G-protein coupled receptors (GPCRs), MT1 (MEL1a) and MT2 (MEL1b). Although a bulk of research has examined the physiopathological effects of MLT, few studies have investigated the selective role played by MT1 and MT2 receptors. Here we have reviewed current knowledge about the implications of MT2 receptors in brain functions. Methods: We searched PubMed, Web of Science, Scopus, Google Scholar and articles reference lists for studies on MT2 receptor ligands in sleep, anxiety, neuropsychiatric diseases and psychopharmacology, including genetic studies on the MTNR1B gene, which encodes the melatonin MT2 receptor. Results: These studies demonstrate that MT2 receptors are involved in the pathophysiology and pharmacology of sleep disorders, anxiety, depression, Alzheimer disease and pain and that selective MT2 receptor agonists show hypnotic and anxiolytic properties. Limitations: Studies examining the role of MT2 receptors in psychopharmacology are still limited. Conclusion: The development of novel selective MT2 receptor ligands, together with further preclinical in vivo studies, may clarify the role of this receptor in brain function and psychopharmacology. The superfamily of GPCRs has proven to be among the most successful drug targets and, consequently, MT2 receptors have great potential for pioneer drug discovery in the treatment of mental diseases for which limited therapeutic targets are currently available. [ABSTRACT FROM AUTHOR]
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- 2014
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35. Phytochemical and Antioxidant-Related Investigations on Bark of Abies spectabilis (D. Don) Spach. from Nepal.
- Author
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Dall'Acqua, Stefano, Minesso, Paola, Shresta, Bharat Babu, Comai, Stefano, Jha, Pramod Kumar, Gewali, Mohan Bikram, Greco, Emanuela, Cervellati, Rinaldo, and Innocenti, Gabbriella
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PHENOLS ,ANTIOXIDANTS ,TIMBER ,PHYTOCHEMICALS ,WASTE products - Abstract
The bark of several coniferous species, a waste product of the timber industry, contains significant amounts of natural antioxidants. In our ongoing studies of Nepalese medicinal plants, we examined the bark from Abies spectabilis as the starting material for extracting antioxidant compounds. In vitro antioxidant activity evaluated by means of three antioxidant methods, namely 2,2-diphenyl-1-picrylhydrazyl (DPPH), Briggs-Rauscher oscillating reaction (BR) and Trolox Equivalent Antioxidant Capacity (TEAC) and total phenol contents with the Folin-Ciocalteau reagent; the ferrous iron chelating capacity was also assessed. The methanol extract of A. spectabilis showed significant antioxidant activity and polyphenol contents (IC
50 4.13 μg/mL, 0.20 μg/mL eq. resorcinol, 4.22 mM eq. Trolox, 3.9 μg/g eq. gallic Acid in the DPPH, BR, TEAC and Folin-Ciocalteau tests, respectively) and weak Fe2+ chelating capacity. Phytochemical studies were also carried out with 1D- and 2D NMR experiments and DI-ESI-MS, HPLC-DAD and LC-MSn measurements. Oligomeric C-type proanthocyanidins, mainly trimeric gallocatechin derivatives, were the most abundant compounds (16% of extract expressed as procyanindin B1). Gallocatechin oligomers (up to six units) and prodelphynidin-gallocatechin polymers were also identified in the extract. Prodelphynidin B4, cyclograndisolide and trans-docosanil ferulate were also isolated and characterized by NMR and MS spectroscopy. [ABSTRACT FROM AUTHOR]- Published
- 2012
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36. Promotion of Non-Rapid Eye Movement Sleep and Activation of Reticular Thalamic Neurons by a Novel MT2 Melatonin Receptor Ligand.
- Author
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Ochoa-Sanchez, Rafael, Comai, Stefano, Lacoste, Baptiste, Bambico, Francis Rodriguez, Dominguez-Lopez, Sergio, Spadoni, Gilberto, Rivara, Silvia, Bedini, Annalida, Angeloni, Debora, Fraschini, Franco, Mor, Marco, Tarzia, Giorgio, Descarries, Laurent, and Gobbi, Gabriella
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- *
MELATONIN , *RAPID eye movement sleep , *RETICULAR formation , *THALAMUS , *NEURONS , *HORMONE receptors , *LIGANDS (Biochemistry) - Abstract
Melatonin activates two brain G-protein coupled receptors, MT1 and MT2 , whose differential roles in the sleep-wake cycle remain to be defined. The novel MT2 receptor partial agonist, N-{2-[(3-methoxyphenyl) phenylamino] ethyl} acetamide (UCM765), is here shown to selectively promote non-rapid eye movement sleep (NREMS) in rats and mice. The enhancement ofNREMSby UCM765 is nullified by the pharmacological blockade or genetic deletion of MT2 receptors.MT2 , but not MT1 , knock-out mice show a decrease in NREMS compared to the wild strain. Immunohistochemical labeling reveals that MT2 receptors are localized in sleep-related brain regions, and notably the reticular thalamic nucleus (Rt). Microinfusion of UCM765 in the Rt promotes NREMS, and its systemic administration induces an increase in firing and rhythmic burst activity of Rt neurons, which is blocked by the MT2 antagonist 4-phenyl-2-propionamidotetralin. Since developing hypnotics that increase NREMS without altering sleep architecture remains a medical challenge, MT2 receptors may represent a novel target for the treatment of sleep disorders. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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37. Tryptophan Metabolites, Cytokines, and Fatty Acid Binding Protein 2 in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.
- Author
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Simonato, Manuela, Dall'Acqua, Stefano, Zilli, Caterina, Sut, Stefania, Tenconi, Romano, Gallo, Nicoletta, Sfriso, Paolo, Sartori, Leonardo, Cavallin, Francesco, Fiocco, Ugo, Cogo, Paola, Agostinis, Paolo, Aldovini, Anna, Bruttomesso, Daniela, Marcolongo, Renzo, Comai, Stefano, and Baritussio, Aldo
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CHRONIC fatigue syndrome ,CARRIER proteins ,TRYPTOPHAN ,FATTY acids ,METABOLITES - Abstract
Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) differ for triggers, mode of start, associated symptoms, evolution, and biochemical traits. Therefore, serious attempts are underway to partition them into subgroups useful for a personalized medicine approach to the disease. Here, we investigated clinical and biochemical traits in 40 ME/CFS patients and 40 sex- and age-matched healthy controls. Particularly, we analyzed serum levels of some cytokines, Fatty Acid Binding Protein 2 (FAPB-2), tryptophan, and some of its metabolites via serotonin and kynurenine. ME/CFS patients were heterogeneous for genetic background, trigger, start mode, symptoms, and evolution. ME/CFS patients had higher levels of IL-17A (p = 0.018), FABP-2 (p = 0.002), and 3-hydroxykynurenine (p = 0.037) and lower levels of kynurenine (p = 0.012) and serotonin (p = 0.045) than controls. Changes in kynurenine and 3-hydroxykynurenine were associated with increased kynurenic acid/kynurenine and 3-hydroxykynurenine/kynurenine ratios, indirect measures of kynurenine aminotransferases and kynurenine 3-monooxygenase enzymatic activities, respectively. No correlation was found among cytokines, FABP-2, and tryptophan metabolites, suggesting that inflammation, anomalies of the intestinal barrier, and changes of tryptophan metabolism may be independently associated with the pathogenesis of the disease. Interestingly, patients with the start of the disease after infection showed lower levels of kynurenine (p = 0.034) than those not starting after an infection. Changes in tryptophan metabolites and increased IL-17A levels in ME/CFS could both be compatible with anomalies in the sphere of energy metabolism. Overall, clinical traits together with serum biomarkers related to inflammation, intestine function, and tryptophan metabolism deserve to be further considered for the development of personalized medicine strategies for ME/CFS. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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38. Early Dysfunction of Substantia Nigra Dopamine Neurons in the ParkinQ311X Mouse.
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Regoni, Maria, Zanetti, Letizia, Comai, Stefano, Mercatelli, Daniela, Novello, Salvatore, Albanese, Federica, Croci, Laura, Consalez, Gian Giacomo, Ciammola, Andrea, Valtorta, Flavia, Morari, Michele, Sassone, Jenny, and Ekker, Marc
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DOPAMINERGIC neurons ,SUBSTANTIA nigra ,DOPAMINE receptors ,PARKIN (Protein) ,LABORATORY mice ,MICE - Abstract
Mutations in the PARK2 gene encoding the protein parkin cause autosomal recessive juvenile parkinsonism (ARJP), a neurodegenerative disease characterized by early dysfunction and loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNc). No therapy is currently available to prevent or slow down the neurodegeneration in ARJP patients. Preclinical models are key to clarifying the early events that lead to neurodegeneration and reveal the potential of novel neuroprotective strategies. ParkinQ311X is a transgenic mouse model expressing in DA neurons a mutant parkin variant found in ARJP patients. This model was previously reported to show the neuropathological hallmark of the disease, i.e., the progressive loss of DA neurons. However, the early dysfunctions that precede neurodegeneration have never been investigated. Here, we analyzed SNc DA neurons in parkinQ311X mice and found early features of mitochondrial dysfunction, extensive cytoplasmic vacuolization, and dysregulation of spontaneous in vivo firing activity. These data suggest that the parkinQ311X mouse recapitulates key features of ARJP and provides a useful tool for studying the neurodegenerative mechanisms underlying the human disease and for screening potential neuroprotective drugs. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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39. Melatonin MT1 and MT2 Receptors Exhibit Distinct Effects in the Modulation of Body Temperature across the Light/Dark Cycle.
- Author
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López-Canul, Martha, Min, Seung Hyun, Posa, Luca, De Gregorio, Danilo, Bedini, Annalida, Spadoni, Gilberto, Gobbi, Gabriella, and Comai, Stefano
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MELATONIN ,BODY temperature ,CIRCADIAN rhythms ,G protein coupled receptors ,PRAZOSIN - Abstract
Melatonin (MLT) is a neurohormone that regulates many physiological functions including sleep, pain, thermoregulation, and circadian rhythms. MLT acts mainly through two G-protein-coupled receptors named MT
1 and MT2 , but also through an MLT type-3 receptor (MT3 ). However, the role of MLT receptor subtypes in thermoregulation is still unknown. We have thus investigated the effects of selective and non-selective MLT receptor agonists/antagonists on body temperature (Tb ) in rats across the 12/12-h light–dark cycle. Rectal temperature was measured every 15 min from 4:00 a.m. to 9:30 a.m. and from 4:00 p.m. to 9:30 p.m., following subcutaneous injection of each compound at either 5:00 a.m. or 5:00 p.m. MLT (40 mg/kg) had no effect when injected at 5 a.m., whereas it decreased Tb during the light phase only when injected at 5:00 p.m. This effect was blocked by the selective MT2 receptor antagonist 4P-PDOT and the non-selective MT1 /MT2 receptor antagonist, luzindole, but not by the α1 /MT3 receptors antagonist prazosin. However, unlike MLT, neither the selective MT1 receptor partial agonist UCM871 (14 mg/kg) nor the selective MT2 partial agonist UCM924 (40 mg/kg) altered Tb during the light phase. In contrast, UCM871 injected at 5:00 p.m. increased Tb at the beginning of the dark phase, whereas UCM924 injected at 5:00 a.m. decreased Tb at the end of the dark phase. These effects were blocked by luzindole and 4P-PDOT, respectively. The MT3 receptor agonist GR135531 (10 mg/kg) did not affect Tb . These data suggest that the simultaneous activation of both MT1 and MT2 receptors is necessary to regulate Tb during the light phase, whereas in a complex but yet unknown manner, they regulate Tb differently during the dark phase. Overall, MT1 and MT2 receptors display complementary but also distinct roles in modulating circadian fluctuations of Tb . [ABSTRACT FROM AUTHOR]- Published
- 2019
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40. Melancholic-Like Behaviors and Circadian Neurobiological Abnormalities in Melatonin MT1 Receptor Knockout Mice.
- Author
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Comai, Stefano, Ochoa-Sanchez, Rafael, Dominguez-Lopez, Sergio, Bambico, Francis Rodriguez, and Gobbi, Gabriella
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MENTAL depression ,NERVOUS system abnormalities ,MELATONIN ,LABORATORY mice ,PHENOTYPES - Abstract
Background: Melancholic depression, described also as endogenous depression, is a mood disorder with distinctive specific psychopathological features and biological homogeneity, including anhedonia, circadian variation of mood, psychomotor activation, weight loss, diurnal cortisol changes, and sleep disturbances. Although several hypotheses have been proposed, the etiology of this disorder is still unknown. Methods: Behavioral, electrophysiological and biochemical approaches were used to characterize the emotional phenotype, serotonergic and noradrenergic electrical activity, and corticosterone in melatonin MT1 receptor knockout mice and their wild type counterparts, during both light and dark phases. Results: Melatonin MT1 receptor knockout mice have decreased mobility in the forced swim and tail suspension tests as well as decreased sucrose consumption, mostly during the dark/inactive phase. These mood variations are reversed by chronic treatment with the tricyclic antidepressant desipramine. In addition, MT1 receptor knockout mice exhibit psychomotor disturbances, higher serum levels of corticosterone the dark phase, and a blunted circadian variation of corticosterone levels. In vivo electrophysiological recordings show a decreased burst-firing activity of locus coeruleus norepinephrine neurons during the dark phase. The circadian physiological variation in the spontaneous firing activity of high-firing neuronal subpopulations of both norepinephrine neurons and dorsal raphe serotonin neurons are abolished in MT1 knockout mice. Conclusions: These data demonstrate that melatonin MT1 receptor knockout mice recapitulate several behavioral and neurobiological circadian changes of human melancholic depression and, for the first time, suggest that the MT1 receptor may be implicated in the pathogenesis of melancholic depression and is a potential pharmacological target for this mental condition. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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41. Cortisol and Oxytocin Could Predict Covert Aggression in Some Psychotic Patients.
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Popescu, Elena Rodica, Semeniuc, Suzana, Hritcu, Luminita Diana, Horhogea, Cristina Elena, Spataru, Mihaela Claudia, Trus, Constantin, Dobrin, Romeo Petru, Chirita, Vasile, and Chirita, Roxana
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HYDROCORTISONE ,OXYTOCIN ,AGGRESSION (Psychology) ,SUBSTANCE abuse ,PERSONALITY disorders - Abstract
Background: The covert or indirect type of aggression has a risk of converting in violent acts and, considering that, it is very important to identify it in order to apply effective preventive measures. In cases of psychotic patients, the risk of becoming violent is harder to predict, as even neuter stimuli may be perceived as threat and trigger aggression. Treating all the psychiatric patients as potential aggressive subjects is not the best preventive measure as only a few of them are aggressive and this measure may further enhance the stigma on mentally ill patients. There is a current need for better understanding of covert aggression and to find objective measures, such as biological markers, that could be indicative of potential violent behavior. In this work, we try to investigate the role of cortisol and oxytocin as potential biomarkers of aggression in patients with psychosis. Material and Methods: We analyzed the level of peripheral oxytocin (pg/mL) and cortisol level (ng/mL) in 28 psychotic patients (they were not on psychotropic treatment at the moment of admission and those with substance abuse or personality disorder were excluded from the study) and correlated it with the intensity of aggression reported by the patient (overt and covert type) using the Overt Covert Aggression Inventory and the level of observed aggression of the patient in the past 7 days (rated by the health care provider) using the Modified Overt Aggression Scale. Results: We found that psychotic patients with a higher level of covert aggression had a lower level of cortisol (61.05 ± 8.04 ng/mL vs. 216.33 ± 12.6.9 ng/mL, p < 0.01) and a higher level of oxytocin (102.87 ± 39.26 vs. 70.01 ± 25.07, p = 0.01) when compared with patients with a lower level of covert aggression. Furthermore, we observed significant negative correlation between cortisol and covert aggression (r = -0.676, p < 0.001) and between oxytocin and covert type of aggression (r = 0.382, p = 0.04). Moreover, we found that a lower level of cortisol together with a higher level of oxytocin are significant predictors of a style of internalized manifestation of aggression, with the predictive model explaining 55% of the variant of the internalized manifestation of aggression (F (2.25) = 17.6, p < 0.001, β = 0.35, R2 = 55.2). We did not find significant correlations between cortisol and overt aggression, and neither between oxytocin and overt aggression. Positive correlations were also found between the overt type of self-reported aggression and overt aggression reported by the rater (r = 0.459, p = 0.01). Conclusions: The importance of a predictive model in understanding covert aggression is imperative and the results of our study show that oxytocin and cortisol warrant to be further investigated in establishing a definitive predictive model for covert aggression. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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42. Mediterranean Diet Adherence and Eating Disorders in Spanish Nurses with Shift Patterns: A Cross-Sectional Study.
- Author
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Leyva-Vela, Belén, Reche-García, Cristina, Hernández-Morante, Juan José, Martínez-Olcina, María, Miralles-Amorós, Laura, and Martínez-Rodríguez, Alejandro
- Abstract
Background and Objectives: Shift work has a significant influence on the mental health of workers. Nursing is characterised by a rotational work system. This study aimed to determine whether there was a link between adherence to the Mediterranean diet (MD) and the risk of suffering an eating disorder (ED) in nurses according to their work shift. Materials and Methods: A total of 240 women (nurses and nursing assistants) were evaluated and completed the PREDIMED-PLUS questionnaire on adherence to the MD and the EAT-26 (Eating Attitude Test, 26 items). Results: The results indicate that there are no differences in adherence to the MD depending on the work shift, being that adherence to the diet is already low. Statistically significant differences appear depending on the work shift in the following dimensions: restrictive behaviours and bulimia subscales (presenting higher scores in the 7-h rotating shift versus the fixed morning shift or 12-h rotating shift) and for total EAT-26 score. Conclusion: Whilst they do not condition adherence to a MD, the nursing shifts that are the most changing in terms of time patterns may condition restrictive behaviours and compensatory risk behaviours related to an ED. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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43. The Relationship between Affect Integration and Psychopathology in Patients with Personality Disorder: A Cross-Sectional Study.
- Author
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Frederiksen, Christina, Solbakken, Ole André, Licht, Rasmus Wentzer, Jørgensen, Carsten René, Rodrigo-Domingo, Maria, and Telléus, Gry Kjaersdam
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PATHOLOGICAL psychology ,PERSONALITY disorders ,PSYCHOLOGICAL distress ,OUTPATIENT medical care ,PSYCHOTHERAPY - Abstract
Background and Objectives: Emotional dysfunction is considered a key component in personality disorders; however, only few studies have examined the relationship between the two. In this study, emotional dysfunction was operationalized through the Affect Integration Inventory, and the aim was to examine the relationships between the level of affect integration and the levels of symptom distress, interpersonal problems, and personality functioning in patients diagnosed with personality disorder according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition. Materials and Methods: Within a hospital-based psychiatric outpatient setting, 87 patients with personality disorder referred for treatment were identified for assessment with the Affect Integration Inventory and other measures (e.g., the Symptom Checklist-90, Revised, the Inventory of Interpersonal Problems 64 circumplex version, and the Severity Indices of Personality Problems). Results: The analyses revealed that problems with affect integration were strongly and statistically significantly correlated with high levels of symptom distress, interpersonal problems, and maladaptive personality functioning. Additionally, low scores on the Affect Integration Inventory regarding discrete affects were associated with distinct and differentiated patterns of interpersonal problems. Conclusion: Taken together, emotional dysfunction, as measured by the Affect Integration Inventory, appeared to be a central component of the pathological self-organization associated with personality disorder. These findings have several implications for the understanding and psychotherapeutic treatment of personality pathology. Furthermore, they highlight the importance of considering the integration of discrete affects and their specific contributions in the conceptualization and treatment of emotional dysfunction in patients with personality disorders. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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44. Acknowledgement to Reviewers of the International Journal of Molecular Sciences in 2014.
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- ABASS, Khaled, ABBOTT, David H., ABE, Naohito
- Abstract
People whom the author would like to thank for their assistance in the creation of the journal includes Khaled Abass, David H. Abbott, and Naohito Abe.
- Published
- 2015
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45. Investigation of the relationship among cortisol, pro-inflammatory cytokines, and the degradation of tryptophan into kynurenine in patients with major depression and suicidal behavior
- Author
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Flavia Valtorta, Gabriella Gobbi, Mirko Manchia, Gaha Lotfi, Douki Wahiba, Stefano Comai, Fadoua Neffati, A. Messaoud, Mensi Rym, Mohamed Fadhel Najjar, Messaoud, Amel, Rym, Mensi, Wahiba, Douki, Neffati, Fadoua, Najjar, Mohamed Fadhel, Gobbi, Gabriella, Manchia, Mirko, Valtorta, Flavia, Lotfi, Gaha, and Comai, Stefano
- Subjects
medicine.medical_specialty ,Hydrocortisone ,inflammatory cytokines ,Inflammation ,cortisol ,Cortisol ,Proinflammatory cytokine ,chemistry.chemical_compound ,Internal medicine ,Drug Discovery ,medicine ,Humans ,Major depression ,tryptophan ratio ,In patient ,Depression (differential diagnoses) ,Kynurenine ,Hypothalamic-pituitary-adrenal (HPA) axis ,suicide ,Depressive Disorder, Major ,Suicide ,Inflammatory cytokines ,business.industry ,Tryptophan ,General Medicine ,medicine.disease ,Interleukin-12 ,Pathophysiology ,Endocrinology ,chemistry ,Major depressive disorder ,Cytokines ,kynurenine/tryptophan ratio ,medicine.symptom ,business ,major depression ,Interleukin-1 - Abstract
Background: The increased degradation of tryptophan (Trp) along the kynurenine (Kyn) pathway due to inflammation and/or activation of the hypothalamic-pituitary–adrenal (HPA) axis has been reported among the biological factors involved in the pathophysiology of major depressive disorder (MDD) and suicide. However, the interaction among these multiple factors is not yet completely clarified. Method: We studied plasma levels of Trp, Kyn, cortisol and proinflammatory cytokines (IL-1, IL- 6, IL-12, IL-20) and calculated the ratio Kyn/Trp as an index of the breakdown of Trp into Kyn in 31 suicidal MDD patients and 67 non-suicidal MDD patients. Result: We confirmed that suicidal MDD patients have reduced plasma Trp, higher Kyn and Kyn/Trp ratio, and no difference in cortisol levels than non-suicidal MDD patients. IL-1 and IL-12 levels were significantly higher in suicidal MDD than in non-suicidal MDD (p=0.034 and p=0.023, respectively), whereas Il-6 and IL-20 levels were equal in the two groups. The Kyn/Trp ratio was positively correlated with a pro-inflammatory cytokines index (r=0.309, p=0.002) and cortisol (r=0.368, p=0.001). Notably, the variance in the Kyn/Trp ratio explained by the model including both cortisol and inflammatory parameters as dependent variables, substantially improved compared with the models in which the two parameters were considered separately. Conclusion: These findings show that both cortisol and proinflammatory cytokines are involved in the enhanced breakdown of Trp into Kyn occurring in suicidal MDD patients, thus adding new knowledge on the biological mechanisms leading to the activation of the Kyn pathway in MDD and suicide.
- Published
- 2021
46. Author Index.
- Subjects
AUTHORS ,NEUROPSYCHOPHARMACOLOGY - Abstract
An author index for the December 2013 issue of the periodical "Neuropsychopharmacology" is presented.
- Published
- 2013
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47. Role of palmitoylethanolamide (PEA) in depression: Translational evidence: Special Section on 'Translational and Neuroscience Studies in Affective Disorders'. Section Editor, Maria Nobile MD, PhD. This Section of JAD focuses on the relevance of translational and neuroscience studies in providing a better understanding of the neural basis of affective disorders. The main aim is to briefly summaries relevant research findings in clinical neuroscience with particular regards to specific innovative topics in mood and anxiety disorders
- Author
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De Gregorio, D., Manchia, M., Carpiniello, B., Valtorta, F., Nobile, M., Gobbi, G., Comai, S., De Gregorio, Danilo, Manchia, Mirko, Carpiniello, Bernardo, Valtorta, Flavia, Nobile, Maria, Gobbi, Gabriella, and Comai, Stefano
- Subjects
Peroxisome proliferator-activated receptor-alpha ,Dietary supplement ,Clinical Psychology ,Depression ,Psychiatry and Mental Health ,Dietary supplements ,Palmitoylethanolamide ,Endocannabinoids ,Endocannabinoid - Abstract
Background: Antidepressants have a low rate of response paired with a delayed onset of action. Translational studies are thus seeking for novel targets for antidepressant drug development. Preclinical evidence has demonstrated that the endocannabinoid system plays an important role in mood and stress response, even if drugs targeting this system have not yet become available for clinical use. The dietary supplement N-Palmitoylethanolamide (PEA) is a fatty acid amide belonging to the endocannabinoid system with potential antidepressant properties. Methods: We performed a bibliographic search to review current knowledge on the potential antidepressant effects of PEA and its underlying mechanism of action. Results: PEA targets not only the peroxisome proliferator-activated receptor-alpha (PPAR-α), but also the endocannabinoid system, binding the G-protein-coupled receptor 55, a non-CB1/CB2 cannabinoid receptor, and also the CB1/CB2 receptors, although with a weak affinity. Preclinical studies have shown antidepressant activity of PEA in animal paradigms of depression and of depression associated with neuropathic pain and traumatic brain injury. In a translational perspective, PEA is increased in stress conditions, and a randomized, double-blind study in depressed patients indicated a fast-antidepressant action of PEA when associated with citalopram. Limitations: There are still limited preclinical and clinical studies investigating the effect of PEA upon the endocannabinoid system and its potential as antidepressant. Conclusions: PEA has potential antidepressant effects alone or in combinations with other classes of antidepressants. Future studies in depressed patients are needed to confirm the mood-modulating properties of PEA and its role as a biomarker of depression.
- Published
- 2019
48. Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain
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Ryan J. McLaughlin, Gabriella Gobbi, Sabatino Maione, Martha Lopez-Canul, Matthew Kaba Aboud, Luca Posa, Stefano Comai, Justine P Enns, Danilo De Gregorio, Rafael Ochoa-Sanchez, De Gregorio, Danilo, Mclaughlin, Ryan J., Posa, Luca, Ochoa-Sanchez, Rafael, Enns, Justine, Lopez-Canul, Martha, Aboud, Matthew, Maione, Sabatino, Comai, Stefano, and Gobbi, Gabriella
- Subjects
Male ,Anxiety ,Cannabidiol ,Dorsal raphe ,Electrophysiology ,Pain ,Pyridines ,Action Potentials ,Pharmacology ,Piperazines ,chemistry.chemical_compound ,0302 clinical medicine ,Piperidines ,030202 anesthesiology ,Ganglia, Spinal ,Allodynia ,Neurology ,Hyperalgesia ,Neuropathic pain ,Serotonin Antagonists ,medicine.symptom ,Capsazepine ,medicine.drug ,Elevated plus maze ,Serotonin ,medicine.drug_class ,TRPV1 ,Anxiolytic ,03 medical and health sciences ,medicine ,Animals ,Rats, Wistar ,Maze Learning ,Swimming ,business.industry ,Antagonist ,Feeding Behavior ,Rats ,Disease Models, Animal ,Lysergic Acid Diethylamide ,Anesthesiology and Pain Medicine ,chemistry ,Exploratory Behavior ,Neuralgia ,Pyrazoles ,Neurology (clinical) ,Capsaicin ,business ,030217 neurology & neurosurgery - Abstract
Clinical studies indicate that cannabidiol (CBD), the primary nonaddictive component of cannabis that interacts with the serotonin (5-HT)1A receptor, may possess analgesic and anxiolytic effects. However, its effects on 5-HT neuronal activity, as well as its impact on models of neuropathic pain are unknown. First, using in vivo single-unit extracellular recordings in rats, we demonstrated that acute intravenous (i.v.) increasing doses of CBD (0.1-1.0 mg/kg) decreased the firing rate of 5-HT neurons in the dorsal raphe nucleus, which was prevented by administration of the 5-HT1A antagonist WAY 100635 (0.3 mg/kg, i.v.) and the TRPV1 antagonist capsazepine (1 mg/kg, i.v.) but not by the CB1 receptor antagonist AM 251 (1 mg/kg, i.v.). Repeated treatment with CBD (5 mg/kg/day, subcutaneously [s.c.], for 7 days) increased 5-HT firing through desensitization of 5-HT1A receptors. Rats subjected to the spared nerve injury model for 24 days showed decreased 5-HT firing activity, mechanical allodynia, and increased anxiety-like behavior in the elevated plus maze test, open-field test, and novelty-suppressed feeding test. Seven days of treatment with CBD reduced mechanical allodynia, decreased anxiety-like behavior, and normalized 5-HT activity. Antiallodynic effects of CBD were fully prevented by capsazepine (10 mg/kg/day, s.c., for 7 days) and partially prevented by WAY 100635 (2 mg/kg/day, s.c., for 7 days), whereas the anxiolytic effect was blocked only by WAY. Overall, repeated treatment with low-dose CBD induces analgesia predominantly through TRPV1 activation, reduces anxiety through 5-HT1A receptor activation, and rescues impaired 5-HT neurotransmission under neuropathic pain conditions.
- Published
- 2019
49. Drugs for insomnia beyond benzodiazepines: Pharmacology, clinical applications, and discovery
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Gabriella Gobbi, Stefano Comai, Tobias Atkin, Atkin, Tobia, Comai, Stefano, and Gobbi, Gabriella
- Subjects
Zolpidem ,Ramelteon ,Pharmacology ,03 medical and health sciences ,Zaleplon ,Benzodiazepines ,0302 clinical medicine ,Sleep Initiation and Maintenance Disorders ,Drug Discovery ,medicine ,Agomelatine ,Humans ,Hypnotics and Sedatives ,Precision Medicine ,Zopiclone ,business.industry ,Suvorexant ,Trazodone ,030227 psychiatry ,Tasimelteon ,Sleep Aids, Pharmaceutical ,Pharmacology, Clinical ,Molecular Medicine ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Although the GABAergic benzodiazepines (BZDs) and Z-drugs (zolpidem, zopiclone, and zaleplon) are FDA-approved for insomnia disorders with a strong evidence base, they have many side effects, including cognitive impairment, tolerance, rebound insomnia upon discontinuation, car accidents/falls, abuse, and dependence liability. Consequently, the clinical use of off-label drugs and novel drugs that do not target the GABAergic system is increasing. The purpose of this review is to analyze the neurobiological and clinical evidence of pharmacological treatments of insomnia, excluding the BZDs and Z-drugs. We analyzed the melatonergic agonist drugs, agomelatine, prolonged-release melatonin, ramelteon, and tasimelteon; the dual orexin receptor antagonist suvorexant; the modulators of the α2δ subunit of voltage-sensitive calcium channels, gabapentin and pregabalin; the H1 antagonist, low-dose doxepin; and the histamine and serotonin receptor antagonists, amitriptyline, mirtazapine, trazodone, olanzapine, and quetiapine. The pharmacology and mechanism of action of these treatments and the evidence-base for the use of these drugs in clinical practice is outlined along with novel pipelines. There is evidence to recommend suvorexant and low-dose doxepin for sleep maintenance insomnia; there is also sufficient evidence to recommend ramelteon for sleep onset insomnia. Although there is limited evidence for the use of the quetiapine, trazodone, mirtazapine, amitriptyline, pregabalin, gabapentin, agomelatine, and olanzapine as treatments for insomnia disorder, these drugs may improve sleep while successfully treating comorbid disorders, with a different side effect profile than the BZDs and Z-drugs. The unique mechanism of action of each drug allows for a more personalized and targeted medical management of insomnia.
- Published
- 2018
50. Translational control of depression-like behavior via phosphorylation of eukaryotic translation initiation factor 4E
- Author
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Christoph Rummel, Mohammad J. Eslamizade, Arnaud Tanti, Naguib Mechawar, Nahum Sonenberg, Vijendra Sharma, Gustavo Turecki, Stefano Comai, Jelena Popic, Edna Matta-Camacho, Giamal N. Luheshi, Nabila Haji, Robert Nadon, Shane Wiebe, Ruifeng Cao, Danilo De Gregorio, Argel Aguilar-Valles, Nicolas A. Nuñez, Gabriella Gobbi, Jean-Claude Lacaille, Aguilar-Valles, Argel, Haji, Nabila, De Gregorio, Danilo, Matta-Camacho, Edna, Eslamizade, Mohammad J., Popic, Jelena, Sharma, Vijendra, Cao, Ruifeng, Rummel, Christoph, Tanti, Arnaud, Wiebe, Shane, Nuñez, Nicola, Comai, Stefano, Nadon, Robert, Luheshi, Giamal, Mechawar, Naguib, Turecki, Gustavo, Lacaille, Jean-Claude, Gobbi, Gabriella, and Sonenberg, Nahum
- Subjects
0301 basic medicine ,Male ,Eukaryotic Initiation Factor-4E ,Serotonin and Noradrenaline Reuptake Inhibitor ,General Physics and Astronomy ,Protein-Serine-Threonine Kinase ,Anxiety ,Synaptic Transmission ,Mice ,0302 clinical medicine ,NF-KappaB Inhibitor alpha ,Phosphorylation ,Serotonin and Noradrenaline Reuptake Inhibitors ,Mice, Knockout ,Multidisciplinary ,Behavior, Animal ,Chemistry ,Depression ,EIF4E ,Chemistry (all) ,Antidepressive Agents ,3. Good health ,Antidepressive Agent ,Tumor necrosis factor alpha ,Female ,Ketamine ,medicine.medical_specialty ,Science ,Citalopram ,Protein Serine-Threonine Kinases ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,Physics and Astronomy (all) ,Dorsal raphe nucleus ,Internal medicine ,Fluoxetine ,medicine ,Animals ,Protein kinase A ,Benzofurans ,Inflammation ,Messenger RNA ,Depressive Disorder, Major ,Biochemistry, Genetics and Molecular Biology (all) ,Protein Biosynthesi ,Animal ,Tumor Necrosis Factor-alpha ,General Chemistry ,Mice, Inbred C57BL ,IκBα ,030104 developmental biology ,Endocrinology ,Protein Biosynthesis ,Benzofuran ,030217 neurology & neurosurgery - Abstract
Translation of mRNA into protein has a fundamental role in neurodevelopment, plasticity, and memory formation; however, its contribution in the pathophysiology of depressive disorders is not fully understood. We investigated the involvement of MNK1/2 (MAPK-interacting serine/threonine-protein kinase 1 and 2) and their target, eIF4E (eukaryotic initiation factor 4E), in depression-like behavior in mice. Mice carrying a mutation in eIF4E for the MNK1/2 phosphorylation site (Ser209Ala, Eif4e ki/ki), the Mnk1/2 double knockout mice (Mnk1/2−/−), or mice treated with the MNK1/2 inhibitor, cercosporamide, displayed anxiety- and depression-like behaviors, impaired serotonin-induced excitatory synaptic activity in the prefrontal cortex, and diminished firing of the dorsal raphe neurons. In Eif4e ki/ki mice, brain IκBα, was decreased, while the NF-κB target, TNFα was elevated. TNFα inhibition in Eif4e ki/ki mice rescued, whereas TNFα administration to wild-type mice mimicked the depression-like behaviors and 5-HT synaptic deficits. We conclude that eIF4E phosphorylation modulates depression-like behavior through regulation of inflammatory responses., Translation of mRNA contributes to neuronal function and complex behaviours, and inflammation is thought to contribute to depression. Here the authors show that mice lacking phosphorylation sites in eIF4E (eukaryotic initiation factor 4E) display anxiety- and depression-like behaviour and decreased IkBα expression; furthermore TNFα delivery to the medial prefrontal cortex induces depression-like behaviour and deficits in serotonergic transmission.
- Published
- 2018
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