The Experts below are selected from a list of 7719 Experts worldwide ranked by ideXlab platform
Francesca Fallarino - One of the best experts on this subject based on the ideXlab platform.
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positive allosteric modulation of indoleamine 2 3 dioxygenase 1 restrains neuroinflammation
Proceedings of the National Academy of Sciences of the United States of America, 2020Co-Authors: Giada Mondanelli, Francesco Antonio Greco, Maria Teresa Pallotta, Ciriana Orabona, Alberta Iacono, Eleonora Panfili, Maria Laura Belladonna, Alice Coletti, Elisa Albini, Francesca FallarinoAbstract:l-tryptophan (Trp), an essential amino acid for mammals, is the precursor of a wide array of immunomodulatory metabolites produced by the kynurenine and Serotonin Pathways. The kynurenine pathway is a paramount source of several immunoregulatory metabolites, including l-kynurenine (Kyn), the main product of indoleamine 2,3-dioxygenase 1 (IDO1) that catalyzes the rate-limiting step of the pathway. In the Serotonin pathway, the metabolite N-acetylSerotonin (NAS) has been shown to possess antioxidant, antiinflammatory, and neuroprotective properties in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). However, little is known about the exact mode of action of the Serotonin metabolite and the possible interplay between the 2 Trp metabolic Pathways. Prompted by the discovery that NAS neuroprotective effects in EAE are abrogated in mice lacking IDO1 expression, we investigated the NAS mode of action in neuroinflammation. We found that NAS directly binds IDO1 and acts as a positive allosteric modulator (PAM) of the IDO1 enzyme in vitro and in vivo. As a result, increased Kyn will activate the ligand-activated transcription factor aryl hydrocarbon receptor and, consequently, antiinflammatory and immunoregulatory effects. Because NAS also increased IDO1 activity in peripheral blood mononuclear cells of a significant proportion of MS patients, our data may set the basis for the development of IDO1 PAMs as first-in-class drugs in autoimmune/neuroinflammatory diseases.
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positive allosteric modulation of indoleamine 2 3 dioxygenase 1 restrains neuroinflammation
Proceedings of the National Academy of Sciences of the United States of America, 2020Co-Authors: Giada Mondanelli, Francesco Antonio Greco, Maria Teresa Pallotta, Ciriana Orabona, Alberta Iacono, Eleonora Panfili, Maria Laura Belladonna, Alice Coletti, Elisa Albini, Francesca FallarinoAbstract:l-tryptophan (Trp), an essential amino acid for mammals, is the precursor of a wide array of immunomodulatory metabolites produced by the kynurenine and Serotonin Pathways. The kynurenine pathway is a paramount source of several immunoregulatory metabolites, including l-kynurenine (Kyn), the main product of indoleamine 2,3-dioxygenase 1 (IDO1) that catalyzes the rate-limiting step of the pathway. In the Serotonin pathway, the metabolite N-acetylSerotonin (NAS) has been shown to possess antioxidant, antiinflammatory, and neuroprotective properties in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). However, little is known about the exact mode of action of the Serotonin metabolite and the possible interplay between the 2 Trp metabolic Pathways. Prompted by the discovery that NAS neuroprotective effects in EAE are abrogated in mice lacking IDO1 expression, we investigated the NAS mode of action in neuroinflammation. We found that NAS directly binds IDO1 and acts as a positive allosteric modulator (PAM) of the IDO1 enzyme in vitro and in vivo. As a result, increased Kyn will activate the ligand-activated transcription factor aryl hydrocarbon receptor and, consequently, antiinflammatory and immunoregulatory effects. Because NAS also increased IDO1 activity in peripheral blood mononuclear cells of a significant proportion of MS patients, our data may set the basis for the development of IDO1 PAMs as first-in-class drugs in autoimmune/neuroinflammatory diseases.
George Battaglia - One of the best experts on this subject based on the ideXlab platform.
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prenatal methamphetamine attenuates Serotonin mediated renin secretion in male and female rat progeny evidence for selective long term dysfunction of Serotonin Pathways in brain
Synapse, 1993Co-Authors: Theresa M Cabrera, Andrew D Levy, L D Van De Kar, George BattagliaAbstract:In adult rats, methamphetamine produces biochemical alterations in brain Serotonin (5-HT) neurons. Since 5-HT is critical to the development of fetal 5-HT neurons and target tissues, we hypothesized that in utero exposure to methamphetamine could result in long-term alterations in postnatal 5-HT systems. Pregnant Sprague-Dawley rats, administered either saline or (+/-)methamphetamine (5 mg/kg, s.c., b.i.d.) from gestational day 13 to 20, were divided into three treatment groups: Saline-injected/Ad Lib Fed (VEH); Saline-injected/Pair Fed (PF); and methamphetamine injected (METH). Prenatal methamphetamine exposure did not alter litter size, gender number, or progeny birth weights. Functional alterations in serotonergic systems were determined in postnatal day (PD) 70 male progeny and in PD 30 female progeny by measuring changes in 5-HT mediated increases in plasma hormones following a single injection of the 5-HT releaser p-chloroamphetamine (PCA; 8 mg/kg). Prenatal methamphetamine produced long-term marked (-30 to -62%) attenuation of plasma renin responses to PCA in male and female progeny. In contrast, no alterations were observed in the ACTH, corticosterone, or prolactin responses to PCA in male and female progeny. Prenatal methamphetamine did not alter basal levels of any hormones measured regardless of gender. No significant differences were observed in the density of cortical or hypothalamic 5-HT uptake sites, or in the density of cortical 5-HT1 or 5-HT2 receptors in male progeny. The lack of significant differences in cortical 5-HT uptake sites observed between PF and METH treated dams 2 days post-parturition indicates that methamphetamine was not neurotoxic to the pregnant dams. These data, which demonstrate longterm postnatal deficits in 5-HT mediated renin secretion, suggest selective functional alterations of brain 5-HT systems in male and female progeny exposed in utero to methamphetamine.
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prenatal cocaine produces deficits in Serotonin mediated neuroendocrine responses in adult rat progeny evidence for long term functional alterations in brain Serotonin Pathways
Synapse, 1993Co-Authors: Theresa M Cabrera, Joseph M Yracheta, Andrew D Levy, L D Van De Kar, George BattagliaAbstract:Cocaine produces biochemical alterations in brain Serotonin (5-HT) neurons. Since 5-HT is critical to the development of fetal 5-HT neurons and target tissues, we hypothesized that in utero exposure to cocaine could result in long-term alterations in postnatal 5-HT systems. Pregnant Sprague-Dawley rats were administered either saline or (-)cocaine (15 mg/kg, s.c., b.i.d.) from gestational day 13 to 20. Prenatal cocaine exposure did not alter litter size, gender number, or progeny birth weights. Functional alterations in serotonergic systems were determined in postnatal day (PD) 70 male progeny by measuring changes in 5-HT mediated plasma hormones following a single 8 mg/kg injection of the 5-HT releaser p-chloroamphetamine (PCA). Cocaine exposed male progeny exhibited significant reductions in adrenocorticotropic hormone (ACTH, -43%) and renin (-62%) responses to PCA. However, no alterations were observed in the corticosterone or prolactin response to PCA. In utero exposure to cocaine did not alter basal levels of ACTH, renin, corticosterone, or prolactin. There were no significant differences in the density of either hypothalamic or cortical 5-HT uptake sites. Likewise, there were no significant differences in the densities of any of the 5-HT1 receptor subtypes or in the density of 5-HT2 receptors in cortex. These data, which provide the first demonstration of deficits in 5-HT mediated neuroendocrine function in adult progeny following in utero exposure to cocaine, indicate long-term functional alterations of brain 5-HT systems.
Jun Sheng - One of the best experts on this subject based on the ideXlab platform.
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caffeine promotes conversion of palmitic acid to palmitoleic acid by inducing expression of fat 5 in caenorhabditis elegans and scd1 in mice
Frontiers in Pharmacology, 2018Co-Authors: Xiaocui Du, Qin Huang, Yun Guan, Ming Lv, Xiaofang He, Chongye Fang, Xuanjun Wang, Jun ShengAbstract:The synthesis and metabolism of fatty acids in an organism is related to many biological processes and is involved in several diseases. The effects of caffeine on fatty acid synthesis and fat storage in Caenorhabditis elegans and mice were studied. After 6 h of food deprivation, adult C. elegans were treated with 0.1 mg/mL caffeine for 24 h. Quantitative reverse-transcription polymerase chain reaction showed that, among all the genes involved in fat accumulation, the mRNA expression of fat-5 in caffeine-treated C. elegans was significantly higher than that of controls, whereas fat-6 and fat-7 displayed no significant difference. Gas chromatography-mass spectrometry was used to verify the fatty acid composition of C. elegans. Results showed that the ratio of palmitoleic acid (16:1) to that of palmitic acid (16:0) was higher in the caffeine-treated group. Several mutant strains, including those involved in the insulin-like growth factor-1, dopamine, and Serotonin Pathways, and nuclear hormone receptors (nhrs), were used to assess their necessity to the effects of caffeine. We found that mdt-15 was essential for the effects of caffeine, which was independent of nhr-49 and nhr-80. Caffeine may increase fat-5 expression by acting on mdt-15. In high fat diet (HFD), but not in normal diet (ND) mice, caffeine induced expression of scd1 in both subcutaneous and epididymal white adipose tissue, which was consistent with the palmitoleic/palmitic ratio results by gas chromatograph analysis. In mature adipocytes, caffeine treatment induced both mRNA and protein expression of scd1 and pgc-1α. Overall, our results provided a possible mechanism on how caffeine modulates metabolism homeostasis in vivo.
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Caffeine Promotes Conversion of Palmitic Acid to Palmitoleic Acid by Inducing Expression of fat-5 in Caenorhabditis elegans and scd1 in Mice
Frontiers in Pharmacology, 2018Co-Authors: Xiaocui Du, Qin Huang, Yun Guan, Ming Lv, Xiaofang He, Chongye Fang, Xuanjun Wang, Jun ShengAbstract:The synthesis and metabolism of fatty acids in an organism is related to many biological processes and is involved in several diseases. The effects of caffeine on fatty acid synthesis and fat storage in Caenorhabditis elegans and mice were studied. After 6 h of food deprivation, adult C. elegans were treated with 0.1 mg/mL caffeine for 24 h. Quantitative reverse-transcription polymerase chain reaction showed that, among all the genes involved in fat accumulation, the mRNA expression of fat-5 in caffeine-treated C. elegans was significantly higher than that of controls, whereas fat-6 and fat-7 displayed no significant difference. Gas chromatography-mass spectrometry was used to verify the fatty acid composition of C. elegans. Results showed that the ratio of palmitoleic acid (16:1) to that of palmitic acid (16:0) was higher in the caffeine-treated group. Several mutant strains, including those involved in the insulin-like growth factor-1, dopamine, and Serotonin Pathways, and nuclear hormone receptors (nhrs), were used to assess their necessity to the effects of caffeine. We found that mdt-15 was essential for the effects of caffeine, which was independent of nhr-49 and nhr-80. Caffeine may increase fat-5 expression by acting on mdt-15. In high fat diet (HFD), but not in normal diet (ND) mice, caffeine induced expression of scd1 in both subcutaneous and epididymal white adipose tissue, which was consistent with the palmitoleic/palmitic ratio results by gas chromatograph analysis.In mature adipocytes, caffeine treatment induced both mRNA and protein expression of scd1 and pgc-1α. Overall, our results provided a possible mechanism on how caffeine modulates metabolism hemeostasis in vivo.
Giada Mondanelli - One of the best experts on this subject based on the ideXlab platform.
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positive allosteric modulation of indoleamine 2 3 dioxygenase 1 restrains neuroinflammation
Proceedings of the National Academy of Sciences of the United States of America, 2020Co-Authors: Giada Mondanelli, Francesco Antonio Greco, Maria Teresa Pallotta, Ciriana Orabona, Alberta Iacono, Eleonora Panfili, Maria Laura Belladonna, Alice Coletti, Elisa Albini, Francesca FallarinoAbstract:l-tryptophan (Trp), an essential amino acid for mammals, is the precursor of a wide array of immunomodulatory metabolites produced by the kynurenine and Serotonin Pathways. The kynurenine pathway is a paramount source of several immunoregulatory metabolites, including l-kynurenine (Kyn), the main product of indoleamine 2,3-dioxygenase 1 (IDO1) that catalyzes the rate-limiting step of the pathway. In the Serotonin pathway, the metabolite N-acetylSerotonin (NAS) has been shown to possess antioxidant, antiinflammatory, and neuroprotective properties in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). However, little is known about the exact mode of action of the Serotonin metabolite and the possible interplay between the 2 Trp metabolic Pathways. Prompted by the discovery that NAS neuroprotective effects in EAE are abrogated in mice lacking IDO1 expression, we investigated the NAS mode of action in neuroinflammation. We found that NAS directly binds IDO1 and acts as a positive allosteric modulator (PAM) of the IDO1 enzyme in vitro and in vivo. As a result, increased Kyn will activate the ligand-activated transcription factor aryl hydrocarbon receptor and, consequently, antiinflammatory and immunoregulatory effects. Because NAS also increased IDO1 activity in peripheral blood mononuclear cells of a significant proportion of MS patients, our data may set the basis for the development of IDO1 PAMs as first-in-class drugs in autoimmune/neuroinflammatory diseases.
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positive allosteric modulation of indoleamine 2 3 dioxygenase 1 restrains neuroinflammation
Proceedings of the National Academy of Sciences of the United States of America, 2020Co-Authors: Giada Mondanelli, Francesco Antonio Greco, Maria Teresa Pallotta, Ciriana Orabona, Alberta Iacono, Eleonora Panfili, Maria Laura Belladonna, Alice Coletti, Elisa Albini, Francesca FallarinoAbstract:l-tryptophan (Trp), an essential amino acid for mammals, is the precursor of a wide array of immunomodulatory metabolites produced by the kynurenine and Serotonin Pathways. The kynurenine pathway is a paramount source of several immunoregulatory metabolites, including l-kynurenine (Kyn), the main product of indoleamine 2,3-dioxygenase 1 (IDO1) that catalyzes the rate-limiting step of the pathway. In the Serotonin pathway, the metabolite N-acetylSerotonin (NAS) has been shown to possess antioxidant, antiinflammatory, and neuroprotective properties in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). However, little is known about the exact mode of action of the Serotonin metabolite and the possible interplay between the 2 Trp metabolic Pathways. Prompted by the discovery that NAS neuroprotective effects in EAE are abrogated in mice lacking IDO1 expression, we investigated the NAS mode of action in neuroinflammation. We found that NAS directly binds IDO1 and acts as a positive allosteric modulator (PAM) of the IDO1 enzyme in vitro and in vivo. As a result, increased Kyn will activate the ligand-activated transcription factor aryl hydrocarbon receptor and, consequently, antiinflammatory and immunoregulatory effects. Because NAS also increased IDO1 activity in peripheral blood mononuclear cells of a significant proportion of MS patients, our data may set the basis for the development of IDO1 PAMs as first-in-class drugs in autoimmune/neuroinflammatory diseases.
Theresa M Cabrera - One of the best experts on this subject based on the ideXlab platform.
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prenatal methamphetamine attenuates Serotonin mediated renin secretion in male and female rat progeny evidence for selective long term dysfunction of Serotonin Pathways in brain
Synapse, 1993Co-Authors: Theresa M Cabrera, Andrew D Levy, L D Van De Kar, George BattagliaAbstract:In adult rats, methamphetamine produces biochemical alterations in brain Serotonin (5-HT) neurons. Since 5-HT is critical to the development of fetal 5-HT neurons and target tissues, we hypothesized that in utero exposure to methamphetamine could result in long-term alterations in postnatal 5-HT systems. Pregnant Sprague-Dawley rats, administered either saline or (+/-)methamphetamine (5 mg/kg, s.c., b.i.d.) from gestational day 13 to 20, were divided into three treatment groups: Saline-injected/Ad Lib Fed (VEH); Saline-injected/Pair Fed (PF); and methamphetamine injected (METH). Prenatal methamphetamine exposure did not alter litter size, gender number, or progeny birth weights. Functional alterations in serotonergic systems were determined in postnatal day (PD) 70 male progeny and in PD 30 female progeny by measuring changes in 5-HT mediated increases in plasma hormones following a single injection of the 5-HT releaser p-chloroamphetamine (PCA; 8 mg/kg). Prenatal methamphetamine produced long-term marked (-30 to -62%) attenuation of plasma renin responses to PCA in male and female progeny. In contrast, no alterations were observed in the ACTH, corticosterone, or prolactin responses to PCA in male and female progeny. Prenatal methamphetamine did not alter basal levels of any hormones measured regardless of gender. No significant differences were observed in the density of cortical or hypothalamic 5-HT uptake sites, or in the density of cortical 5-HT1 or 5-HT2 receptors in male progeny. The lack of significant differences in cortical 5-HT uptake sites observed between PF and METH treated dams 2 days post-parturition indicates that methamphetamine was not neurotoxic to the pregnant dams. These data, which demonstrate longterm postnatal deficits in 5-HT mediated renin secretion, suggest selective functional alterations of brain 5-HT systems in male and female progeny exposed in utero to methamphetamine.
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prenatal cocaine produces deficits in Serotonin mediated neuroendocrine responses in adult rat progeny evidence for long term functional alterations in brain Serotonin Pathways
Synapse, 1993Co-Authors: Theresa M Cabrera, Joseph M Yracheta, Andrew D Levy, L D Van De Kar, George BattagliaAbstract:Cocaine produces biochemical alterations in brain Serotonin (5-HT) neurons. Since 5-HT is critical to the development of fetal 5-HT neurons and target tissues, we hypothesized that in utero exposure to cocaine could result in long-term alterations in postnatal 5-HT systems. Pregnant Sprague-Dawley rats were administered either saline or (-)cocaine (15 mg/kg, s.c., b.i.d.) from gestational day 13 to 20. Prenatal cocaine exposure did not alter litter size, gender number, or progeny birth weights. Functional alterations in serotonergic systems were determined in postnatal day (PD) 70 male progeny by measuring changes in 5-HT mediated plasma hormones following a single 8 mg/kg injection of the 5-HT releaser p-chloroamphetamine (PCA). Cocaine exposed male progeny exhibited significant reductions in adrenocorticotropic hormone (ACTH, -43%) and renin (-62%) responses to PCA. However, no alterations were observed in the corticosterone or prolactin response to PCA. In utero exposure to cocaine did not alter basal levels of ACTH, renin, corticosterone, or prolactin. There were no significant differences in the density of either hypothalamic or cortical 5-HT uptake sites. Likewise, there were no significant differences in the densities of any of the 5-HT1 receptor subtypes or in the density of 5-HT2 receptors in cortex. These data, which provide the first demonstration of deficits in 5-HT mediated neuroendocrine function in adult progeny following in utero exposure to cocaine, indicate long-term functional alterations of brain 5-HT systems.
