The Experts below are selected from a list of 51 Experts worldwide ranked by ideXlab platform
Staci D Bilbo - One of the best experts on this subject based on the ideXlab platform.
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neonatal immune challenge induces female specific changes in social behavior and Somatostatin Cell number
Brain Behavior and Immunity, 2020Co-Authors: Caroline J Smith, Marcy A Kingsbury, Julia E Dziabis, Richa Hanamsagar, Karen E Malacon, Jessica N Tran, Haley A Norris, Mary Gulino, Evan A Bordt, Staci D BilboAbstract:Decreases in social behavior are a hallmark aspect of acute "sickness behavior" in response to infection. However, immune insults that occur during the perinatal period may have long-lasting consequences for adult social behavior by impacting the developmental organization of underlying neural circuits. Microglia, the resident immune Cells of the central nervous system, are sensitive to immune stimulation and play a critical role in the developmental sculpting of neural circuits, making them likely mediators of this process. Here, we investigated the impact of a postnatal day (PND) 4 lipopolysaccharide (LPS) challenge on social behavior in adult mice. Somewhat surprisingly, neonatal LPS treatment decreased sociability in adult female, but not male mice. LPS-treated females also displayed reduced social interaction and social memory in a social discrimination task as compared to saline-treated females. Somatostatin (SST) interneurons within the anterior cingulate cortex (ACC) have recently been suggested to modulate a variety of social behaviors. Interestingly, the female-specific changes in social behavior observed here were accompanied by an increase in SST interneuron number in the ACC. Finally, these changes in social behavior and SST Cell number do not appear to depend on microglial inflammatory signaling, because microglia-specific genetic knock-down of myeloid differentiation response protein 88 (MyD88; the removal of which prevents LPS from increasing proinflammatory cytokines such as TNFα and IL-1β) did not prevent these LPS-induced changes. This study provides novel evidence for enduring effects of neonatal immune activation on social behavior and SST interneurons in females, largely independent of microglial inflammatory signaling.
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neonatal immune challenge induces female specific changes in social behavior and Somatostatin Cell number independent of microglial inflammatory signaling
bioRxiv, 2020Co-Authors: Caroline J Smith, Marcy A Kingsbury, Julia E Dziabis, Richa Hanamsagar, Karen E Malacon, Jessica N Tran, Haley A Norris, Mary Gulino, Staci D BilboAbstract:Decreases in social behavior are a hallmark aspect of acute sickness behavior in response to infection. However, immune insults that occur during the perinatal period may have long-lasting consequences for adult social behavior by impacting the developmental organization of underlying neural circuits. Microglia, the resident immune Cells of the central nervous system, are sensitive to immune stimulation and play a critical role in the developmental sculpting of neural circuits, making them likely mediators of this process. Here, we investigated the impact of a postnatal day (PND) 4 lipopolysaccharide (LPS) challenge on social behavior in adult mice. Somewhat surprisingly, neonatal LPS treatment decreased sociability in adult female, but not male mice. LPS-treated females also displayed reduced social interaction and social memory in a social discrimination task as compared to saline-treated females. Somatostatin (SST) interneurons within the anterior cingulate cortex (ACC) have recently been suggested to modulate a variety of social behaviors. Interestingly, the female-specific changes in social behavior observed here were accompanied by an increase in SST interneuron number in the ACC. Finally, these changes in social behavior and SST Cell number do not appear to depend on microglial inflammatory signaling, because microglia-specific genetic knock-down of myeloid differentiation response protein 88 (MyD88; the removal of which prevents LPS from increasing proinflammatory cytokines such as TNF alpha; and IL-1 beta) did not prevent these LPS-induced changes. This study provides novel evidence for enduring effects of neonatal immune activation on social behavior and SST interneurons in females, independent of microglial inflammatory signaling.
Julien Ghislain - One of the best experts on this subject based on the ideXlab platform.
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free fatty acid receptor 4 inhibitory signaling in delta Cells regulates islet hormone secretion in mice
Molecular metabolism, 2021Co-Authors: Marine L Croze, Marcus F Flisher, Arthur Guillaume, Caroline Tremblay, Glyn M Noguchi, Sabrina Granziera, Kevin Vivot, Vincent C Castillo, Scott A Campbell, Julien GhislainAbstract:Abstract Objective Maintenance of glucose homeostasis requires the precise regulation of hormone secretion from the endocrine pancreas. Free fatty-acid receptor 4 (FFAR4/GPR120) is a G protein-coupled receptor whose activation in islets of Langerhans promotes insulin and glucagon secretion and inhibits Somatostatin secretion. However, the contribution of individual islet Cell types (α, β, and δ Cells) to the insulinotropic and glucagonotropic effects of GPR120 remains unclear. As gpr120 mRNA is enriched in Somatostatin-secreting δ Cells, we hypothesized that GPR120 activation stimulates insulin and glucagon secretion via inhibition of Somatostatin release. Methods Glucose tolerance tests were performed in mice after administration of the selective GPR120 agonist Compound A. Insulin, glucagon and Somatostatin secretion were measured in static incubations of isolated mouse islets in response to endogenous (ω-3 polyunsaturated fatty acids) and/or pharmacological (Compound A and AZ-13581837) GPR120 agonists. The effect of Compound A on hormone secretion was tested further in islets isolated from mice with global or Somatostatin Cell-specific knockout of gpr120. Gpr120 expression was assessed in pancreatic sections by RNA in situ hybridization. Cyclic AMP (cAMP) and calcium dynamics in response to pharmacological GPR120 agonists were measured specifically in α, β and δ Cells in intact islets using cAMPER and GCaMP6 reporter mice, respectively. Results Acute exposure to Compound A increased glucose tolerance and circulating insulin and glucagon levels in vivo. Endogenous and/or pharmacological and GPR120 agonists reduced Somatostatin secretion in isolated islets and concomitantly demonstrated dose-dependent potentiation of glucose-stimulated insulin secretion and arginine-stimulated glucagon secretion. Gpr120 was enriched in δ Cells. Pharmacological GPR120 agonists reduced cAMP and calcium levels in δ Cells but increased these signals in α and β Cells. Compound A-mediated inhibition of Somatostatin secretion was insensitive to pertussis toxin. The effect of Compound A on hormone secretion was completely absent in islets from mice with either global or Somatostatin Cell-specific deletion of gpr120 and was partially reduced upon blockade of Somatostatin receptor signaling by cycloSomatostatin. Conclusions Inhibitory GPR120 signaling in δ Cells contributes to both insulin and glucagon secretion in part via mitigating Somatostatin release.
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free fatty acid receptor 4 inhibitory signaling in delta Cells regulates islet hormone secretion in mice
bioRxiv, 2020Co-Authors: Marine L Croze, Marcus F Flisher, Arthur Guillaume, Caroline Tremblay, Glyn M Noguchi, Sabrina Granziera, Kevin Vivot, Vincent C Castillo, Scott A Campbell, Julien GhislainAbstract:Objective: Maintenance of glucose homeostasis requires the precise regulation of hormone secretion from the endocrine pancreas. Free-fatty acid receptor 4 (FFAR4/GPR120) is a G protein-coupled receptor whose activation in islets of Langerhans promotes insulin and glucagon secretion and inhibits Somatostatin secretion. However, the contribution of individual islet Cell types (alpha, beta, and delta Cells) to the insulinotropic and glucagonotropic effects of GPR120 remains unclear. As gpr120 mRNA is enriched in Somatostatin-secreting delta Cells, we hypothesized that GPR120 activation stimulates insulin and glucagon secretion via inhibition of Somatostatin release. Methods: Glucose tolerance tests were performed in mice after administration of the selective GPR120 agonist Compound A. Insulin, glucagon and Somatostatin secretion were measured in static incubations of isolated mouse islets in response to endogenous (ω-3 polyunsaturated fatty acids) and/or pharmacological (Compound A and AZ-13581837) GPR120 agonists. The effect of Compound A on hormone secretion was tested further in islets isolated from mice with global or Somatostatin Cell-specific knockout of gpr120. Gpr120 expression was assessed in pancreatic section by RNA in situ hybridization and immunohistochemistry. Cyclic AMP (cAMP) and calcium dynamics in response to pharmacological GPR120 agonists were measured specifically in alpha, beta and delta Cells in intact islets using cAMPER and GCaMP6 reporter mice, respectively. Results: Acute exposure to Compound A increased glucose tolerance and circulating insulin and glucagon levels in vivo. Endogenous and/or pharmacological and GPR120 agonists reduced Somatostatin secretion in isolated islets and concomitantly demonstrated dose-dependent potentiation of glucose-stimulated insulin secretion and arginine-stimulated glucagon secretion. GPR120 was enriched in delta Cells and pharmacological GPR120 agonists reduced cAMP and calcium levels in delta Cells, but increased these signals in alpha and beta Cells. Compound A-mediated inhibition of Somatostatin secretion was insensitive to pertussis toxin. The effect of Compound A on hormone secretion was completely absent in islets from mice with either global or Somatostatin Cell-specific deletion of gpr120 and was partially reduced upon blockade of Somatostatin receptor signaling by cycloSomatostatin. Conclusions: Inhibitory GPR120 signaling in delta Cells contributes to both insulin and glucagon secretion in part via mitigating Somatostatin release.
Caroline J Smith - One of the best experts on this subject based on the ideXlab platform.
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neonatal immune challenge induces female specific changes in social behavior and Somatostatin Cell number
Brain Behavior and Immunity, 2020Co-Authors: Caroline J Smith, Marcy A Kingsbury, Julia E Dziabis, Richa Hanamsagar, Karen E Malacon, Jessica N Tran, Haley A Norris, Mary Gulino, Evan A Bordt, Staci D BilboAbstract:Decreases in social behavior are a hallmark aspect of acute "sickness behavior" in response to infection. However, immune insults that occur during the perinatal period may have long-lasting consequences for adult social behavior by impacting the developmental organization of underlying neural circuits. Microglia, the resident immune Cells of the central nervous system, are sensitive to immune stimulation and play a critical role in the developmental sculpting of neural circuits, making them likely mediators of this process. Here, we investigated the impact of a postnatal day (PND) 4 lipopolysaccharide (LPS) challenge on social behavior in adult mice. Somewhat surprisingly, neonatal LPS treatment decreased sociability in adult female, but not male mice. LPS-treated females also displayed reduced social interaction and social memory in a social discrimination task as compared to saline-treated females. Somatostatin (SST) interneurons within the anterior cingulate cortex (ACC) have recently been suggested to modulate a variety of social behaviors. Interestingly, the female-specific changes in social behavior observed here were accompanied by an increase in SST interneuron number in the ACC. Finally, these changes in social behavior and SST Cell number do not appear to depend on microglial inflammatory signaling, because microglia-specific genetic knock-down of myeloid differentiation response protein 88 (MyD88; the removal of which prevents LPS from increasing proinflammatory cytokines such as TNFα and IL-1β) did not prevent these LPS-induced changes. This study provides novel evidence for enduring effects of neonatal immune activation on social behavior and SST interneurons in females, largely independent of microglial inflammatory signaling.
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neonatal immune challenge induces female specific changes in social behavior and Somatostatin Cell number independent of microglial inflammatory signaling
bioRxiv, 2020Co-Authors: Caroline J Smith, Marcy A Kingsbury, Julia E Dziabis, Richa Hanamsagar, Karen E Malacon, Jessica N Tran, Haley A Norris, Mary Gulino, Staci D BilboAbstract:Decreases in social behavior are a hallmark aspect of acute sickness behavior in response to infection. However, immune insults that occur during the perinatal period may have long-lasting consequences for adult social behavior by impacting the developmental organization of underlying neural circuits. Microglia, the resident immune Cells of the central nervous system, are sensitive to immune stimulation and play a critical role in the developmental sculpting of neural circuits, making them likely mediators of this process. Here, we investigated the impact of a postnatal day (PND) 4 lipopolysaccharide (LPS) challenge on social behavior in adult mice. Somewhat surprisingly, neonatal LPS treatment decreased sociability in adult female, but not male mice. LPS-treated females also displayed reduced social interaction and social memory in a social discrimination task as compared to saline-treated females. Somatostatin (SST) interneurons within the anterior cingulate cortex (ACC) have recently been suggested to modulate a variety of social behaviors. Interestingly, the female-specific changes in social behavior observed here were accompanied by an increase in SST interneuron number in the ACC. Finally, these changes in social behavior and SST Cell number do not appear to depend on microglial inflammatory signaling, because microglia-specific genetic knock-down of myeloid differentiation response protein 88 (MyD88; the removal of which prevents LPS from increasing proinflammatory cytokines such as TNF alpha; and IL-1 beta) did not prevent these LPS-induced changes. This study provides novel evidence for enduring effects of neonatal immune activation on social behavior and SST interneurons in females, independent of microglial inflammatory signaling.
Marine L Croze - One of the best experts on this subject based on the ideXlab platform.
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free fatty acid receptor 4 inhibitory signaling in delta Cells regulates islet hormone secretion in mice
Molecular metabolism, 2021Co-Authors: Marine L Croze, Marcus F Flisher, Arthur Guillaume, Caroline Tremblay, Glyn M Noguchi, Sabrina Granziera, Kevin Vivot, Vincent C Castillo, Scott A Campbell, Julien GhislainAbstract:Abstract Objective Maintenance of glucose homeostasis requires the precise regulation of hormone secretion from the endocrine pancreas. Free fatty-acid receptor 4 (FFAR4/GPR120) is a G protein-coupled receptor whose activation in islets of Langerhans promotes insulin and glucagon secretion and inhibits Somatostatin secretion. However, the contribution of individual islet Cell types (α, β, and δ Cells) to the insulinotropic and glucagonotropic effects of GPR120 remains unclear. As gpr120 mRNA is enriched in Somatostatin-secreting δ Cells, we hypothesized that GPR120 activation stimulates insulin and glucagon secretion via inhibition of Somatostatin release. Methods Glucose tolerance tests were performed in mice after administration of the selective GPR120 agonist Compound A. Insulin, glucagon and Somatostatin secretion were measured in static incubations of isolated mouse islets in response to endogenous (ω-3 polyunsaturated fatty acids) and/or pharmacological (Compound A and AZ-13581837) GPR120 agonists. The effect of Compound A on hormone secretion was tested further in islets isolated from mice with global or Somatostatin Cell-specific knockout of gpr120. Gpr120 expression was assessed in pancreatic sections by RNA in situ hybridization. Cyclic AMP (cAMP) and calcium dynamics in response to pharmacological GPR120 agonists were measured specifically in α, β and δ Cells in intact islets using cAMPER and GCaMP6 reporter mice, respectively. Results Acute exposure to Compound A increased glucose tolerance and circulating insulin and glucagon levels in vivo. Endogenous and/or pharmacological and GPR120 agonists reduced Somatostatin secretion in isolated islets and concomitantly demonstrated dose-dependent potentiation of glucose-stimulated insulin secretion and arginine-stimulated glucagon secretion. Gpr120 was enriched in δ Cells. Pharmacological GPR120 agonists reduced cAMP and calcium levels in δ Cells but increased these signals in α and β Cells. Compound A-mediated inhibition of Somatostatin secretion was insensitive to pertussis toxin. The effect of Compound A on hormone secretion was completely absent in islets from mice with either global or Somatostatin Cell-specific deletion of gpr120 and was partially reduced upon blockade of Somatostatin receptor signaling by cycloSomatostatin. Conclusions Inhibitory GPR120 signaling in δ Cells contributes to both insulin and glucagon secretion in part via mitigating Somatostatin release.
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free fatty acid receptor 4 inhibitory signaling in delta Cells regulates islet hormone secretion in mice
bioRxiv, 2020Co-Authors: Marine L Croze, Marcus F Flisher, Arthur Guillaume, Caroline Tremblay, Glyn M Noguchi, Sabrina Granziera, Kevin Vivot, Vincent C Castillo, Scott A Campbell, Julien GhislainAbstract:Objective: Maintenance of glucose homeostasis requires the precise regulation of hormone secretion from the endocrine pancreas. Free-fatty acid receptor 4 (FFAR4/GPR120) is a G protein-coupled receptor whose activation in islets of Langerhans promotes insulin and glucagon secretion and inhibits Somatostatin secretion. However, the contribution of individual islet Cell types (alpha, beta, and delta Cells) to the insulinotropic and glucagonotropic effects of GPR120 remains unclear. As gpr120 mRNA is enriched in Somatostatin-secreting delta Cells, we hypothesized that GPR120 activation stimulates insulin and glucagon secretion via inhibition of Somatostatin release. Methods: Glucose tolerance tests were performed in mice after administration of the selective GPR120 agonist Compound A. Insulin, glucagon and Somatostatin secretion were measured in static incubations of isolated mouse islets in response to endogenous (ω-3 polyunsaturated fatty acids) and/or pharmacological (Compound A and AZ-13581837) GPR120 agonists. The effect of Compound A on hormone secretion was tested further in islets isolated from mice with global or Somatostatin Cell-specific knockout of gpr120. Gpr120 expression was assessed in pancreatic section by RNA in situ hybridization and immunohistochemistry. Cyclic AMP (cAMP) and calcium dynamics in response to pharmacological GPR120 agonists were measured specifically in alpha, beta and delta Cells in intact islets using cAMPER and GCaMP6 reporter mice, respectively. Results: Acute exposure to Compound A increased glucose tolerance and circulating insulin and glucagon levels in vivo. Endogenous and/or pharmacological and GPR120 agonists reduced Somatostatin secretion in isolated islets and concomitantly demonstrated dose-dependent potentiation of glucose-stimulated insulin secretion and arginine-stimulated glucagon secretion. GPR120 was enriched in delta Cells and pharmacological GPR120 agonists reduced cAMP and calcium levels in delta Cells, but increased these signals in alpha and beta Cells. Compound A-mediated inhibition of Somatostatin secretion was insensitive to pertussis toxin. The effect of Compound A on hormone secretion was completely absent in islets from mice with either global or Somatostatin Cell-specific deletion of gpr120 and was partially reduced upon blockade of Somatostatin receptor signaling by cycloSomatostatin. Conclusions: Inhibitory GPR120 signaling in delta Cells contributes to both insulin and glucagon secretion in part via mitigating Somatostatin release.
Karen E Malacon - One of the best experts on this subject based on the ideXlab platform.
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neonatal immune challenge induces female specific changes in social behavior and Somatostatin Cell number
Brain Behavior and Immunity, 2020Co-Authors: Caroline J Smith, Marcy A Kingsbury, Julia E Dziabis, Richa Hanamsagar, Karen E Malacon, Jessica N Tran, Haley A Norris, Mary Gulino, Evan A Bordt, Staci D BilboAbstract:Decreases in social behavior are a hallmark aspect of acute "sickness behavior" in response to infection. However, immune insults that occur during the perinatal period may have long-lasting consequences for adult social behavior by impacting the developmental organization of underlying neural circuits. Microglia, the resident immune Cells of the central nervous system, are sensitive to immune stimulation and play a critical role in the developmental sculpting of neural circuits, making them likely mediators of this process. Here, we investigated the impact of a postnatal day (PND) 4 lipopolysaccharide (LPS) challenge on social behavior in adult mice. Somewhat surprisingly, neonatal LPS treatment decreased sociability in adult female, but not male mice. LPS-treated females also displayed reduced social interaction and social memory in a social discrimination task as compared to saline-treated females. Somatostatin (SST) interneurons within the anterior cingulate cortex (ACC) have recently been suggested to modulate a variety of social behaviors. Interestingly, the female-specific changes in social behavior observed here were accompanied by an increase in SST interneuron number in the ACC. Finally, these changes in social behavior and SST Cell number do not appear to depend on microglial inflammatory signaling, because microglia-specific genetic knock-down of myeloid differentiation response protein 88 (MyD88; the removal of which prevents LPS from increasing proinflammatory cytokines such as TNFα and IL-1β) did not prevent these LPS-induced changes. This study provides novel evidence for enduring effects of neonatal immune activation on social behavior and SST interneurons in females, largely independent of microglial inflammatory signaling.
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neonatal immune challenge induces female specific changes in social behavior and Somatostatin Cell number independent of microglial inflammatory signaling
bioRxiv, 2020Co-Authors: Caroline J Smith, Marcy A Kingsbury, Julia E Dziabis, Richa Hanamsagar, Karen E Malacon, Jessica N Tran, Haley A Norris, Mary Gulino, Staci D BilboAbstract:Decreases in social behavior are a hallmark aspect of acute sickness behavior in response to infection. However, immune insults that occur during the perinatal period may have long-lasting consequences for adult social behavior by impacting the developmental organization of underlying neural circuits. Microglia, the resident immune Cells of the central nervous system, are sensitive to immune stimulation and play a critical role in the developmental sculpting of neural circuits, making them likely mediators of this process. Here, we investigated the impact of a postnatal day (PND) 4 lipopolysaccharide (LPS) challenge on social behavior in adult mice. Somewhat surprisingly, neonatal LPS treatment decreased sociability in adult female, but not male mice. LPS-treated females also displayed reduced social interaction and social memory in a social discrimination task as compared to saline-treated females. Somatostatin (SST) interneurons within the anterior cingulate cortex (ACC) have recently been suggested to modulate a variety of social behaviors. Interestingly, the female-specific changes in social behavior observed here were accompanied by an increase in SST interneuron number in the ACC. Finally, these changes in social behavior and SST Cell number do not appear to depend on microglial inflammatory signaling, because microglia-specific genetic knock-down of myeloid differentiation response protein 88 (MyD88; the removal of which prevents LPS from increasing proinflammatory cytokines such as TNF alpha; and IL-1 beta) did not prevent these LPS-induced changes. This study provides novel evidence for enduring effects of neonatal immune activation on social behavior and SST interneurons in females, independent of microglial inflammatory signaling.