Developmental disruption of amygdala transcriptome and socioemotional behavior in rats exposed to valproic acid prenatally / Catherine E. BARRETT in Molecular Autism, 8 (2017)  

Public ISBD [article]  inMolecular Autism > 8 (2017) . - 42p. Titre : Developmental disruption of amygdala transcriptome and socioemotional behavior in rats exposed to valproic acid prenatally Type de document : texte imprimé Auteurs : Catherine E. BARRETT, Auteur ; Thomas M. HENNESSEY, Auteur ; Katelyn M. GORDON, Auteur ; Steve J. RYAN, Auteur ; Morgan L. MCNAIR, Auteur ; Kerry J. RESSLER, Auteur ; Donald G. RAINNIE, Auteur Article en page(s) : 42p. Langues : Anglais (eng) Mots-clés : Autism  Basolateral amygdala  Protein kinase A  Proteomics  RNA sequencing  Social behavior  Transcriptomics  Valproic acid Index. décimale : PER Périodiques Résumé : BACKGROUND: The amygdala controls socioemotional behavior and has consistently been implicated in the etiology of autism spectrum disorder (ASD). Precocious amygdala development is commonly reported in ASD youth with the degree of overgrowth positively correlated to the severity of ASD symptoms. Prenatal exposure to VPA leads to an ASD phenotype in both humans and rats and has become a commonly used tool to model the complexity of ASD symptoms in the laboratory. Here, we examined abnormalities in gene expression in the amygdala and socioemotional behavior across development in the valproic acid (VPA) rat model of ASD. METHODS: Rat dams received oral gavage of VPA (500 mg/kg) or saline daily between E11 and 13. Socioemotional behavior was tracked across development in both sexes. RNA sequencing and proteomics were performed on amygdala samples from male rats across development. RESULTS: Effects of VPA on time spent in social proximity and anxiety-like behavior were sex dependent, with social abnormalities presenting in males and heightened anxiety in females. Across time VPA stunted developmental and immune, but enhanced cellular death and disorder, pathways in the amygdala relative to saline controls. At postnatal day 10, gene pathways involved in nervous system and cellular development displayed predicted activations in prenatally exposed VPA amygdala samples. By juvenile age, however, transcriptomic and proteomic pathways displayed reductions in cellular growth and neural development. Alterations in immune pathways, calcium signaling, Rho GTPases, and protein kinase A signaling were also observed. CONCLUSIONS: As behavioral, developmental, and genomic alterations are similar to those reported in ASD, these results lend support to prenatal exposure to VPA as a useful tool for understanding how developmental insults to molecular pathways in the amygdala give rise to ASD-related syndromes. En ligne : http://dx.doi.org/10.1186/s13229-017-0160-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329 [article] Developmental disruption of amygdala transcriptome and socioemotional behavior in rats exposed to valproic acid prenatally [texte imprimé] / Catherine E. BARRETT, Auteur ; Thomas M. HENNESSEY, Auteur ; Katelyn M. GORDON, Auteur ; Steve J. RYAN, Auteur ; Morgan L. MCNAIR, Auteur ; Kerry J. RESSLER, Auteur ; Donald G. RAINNIE, Auteur . - 42p. Langues : Anglais (eng) in Molecular Autism > 8 (2017) . - 42p. Mots-clés : Autism  Basolateral amygdala  Protein kinase A  Proteomics  RNA sequencing  Social behavior  Transcriptomics  Valproic acid Index. décimale : PER Périodiques Résumé : BACKGROUND: The amygdala controls socioemotional behavior and has consistently been implicated in the etiology of autism spectrum disorder (ASD). Precocious amygdala development is commonly reported in ASD youth with the degree of overgrowth positively correlated to the severity of ASD symptoms. Prenatal exposure to VPA leads to an ASD phenotype in both humans and rats and has become a commonly used tool to model the complexity of ASD symptoms in the laboratory. Here, we examined abnormalities in gene expression in the amygdala and socioemotional behavior across development in the valproic acid (VPA) rat model of ASD. METHODS: Rat dams received oral gavage of VPA (500 mg/kg) or saline daily between E11 and 13. Socioemotional behavior was tracked across development in both sexes. RNA sequencing and proteomics were performed on amygdala samples from male rats across development. RESULTS: Effects of VPA on time spent in social proximity and anxiety-like behavior were sex dependent, with social abnormalities presenting in males and heightened anxiety in females. Across time VPA stunted developmental and immune, but enhanced cellular death and disorder, pathways in the amygdala relative to saline controls. At postnatal day 10, gene pathways involved in nervous system and cellular development displayed predicted activations in prenatally exposed VPA amygdala samples. By juvenile age, however, transcriptomic and proteomic pathways displayed reductions in cellular growth and neural development. Alterations in immune pathways, calcium signaling, Rho GTPases, and protein kinase A signaling were also observed. CONCLUSIONS: As behavioral, developmental, and genomic alterations are similar to those reported in ASD, these results lend support to prenatal exposure to VPA as a useful tool for understanding how developmental insults to molecular pathways in the amygdala give rise to ASD-related syndromes. En ligne : http://dx.doi.org/10.1186/s13229-017-0160-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329

Physiological markers of anxiety are increased in children of abused mothers / Tanja JOVANOVIC in Journal of Child Psychology and Psychiatry, 52-8 (August 2011)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 52-8 (August 2011) . - p.844-852 Titre : Physiological markers of anxiety are increased in children of abused mothers Type de document : texte imprimé Auteurs : Tanja JOVANOVIC, Auteur ; Ami SMITH, Auteur ; Asante KAMKWALALA, Auteur ; James POOLE, Auteur ; Tara SAMPLES, Auteur ; Seth D. NORRHOLM, Auteur ; Kerry J. RESSLER, Auteur ; Bekh BRADLEY, Auteur Année de publication : 2011 Article en page(s) : p.844-852 Langues : Anglais (eng) Mots-clés : Child abuse  maternal trauma  child anxiety  startle response  heart-rate variability Index. décimale : PER Périodiques Résumé : Background:  A growing number of studies indicate that low income, African American men and women living in urban environments are at high risk for trauma exposure, which may have intergenerational effects. The current study employed psychophysiological methods to describe biomarkers of anxiety in children of traumatized mothers. Methods:  Study participants were recruited from a highly traumatized urban population, comprising mother–child pairs (n = 36) that included school-age children. Mothers were assessed for childhood abuse with the Childhood Trauma Questionnaire, as well as symptoms of depression and posttraumatic stress disorder (PTSD). The children were measured for dark-enhanced startle responses and heart-rate variability. Results:  Dark-enhanced startle was found to be higher in children whose mothers had high levels of childhood physical abuse, as compared to children whose mothers had low levels of physical abuse. During the habituation phase of the startle experiment, children whose mothers had high levels of childhood emotional abuse had higher sympathetic system activation compared to children of mothers with low emotional abuse. These effects remained significant after accounting for maternal symptoms of PTSD and depression, as well as for the child’s trauma exposure. Conclusion:  These results demonstrate that children of mothers who have history of childhood physical and emotional abuse have higher dark-enhanced startle as well as greater sympathetic nervous system activation than children of mothers who do not report a history of childhood physical and emotional abuse, and emphasize the utility of physiological measures as pervasive biomarkers of psychopathology that can easily be measured in children. En ligne : http://dx.doi.org/10.1111/j.1469-7610.2011.02410.x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=132 [article] Physiological markers of anxiety are increased in children of abused mothers [texte imprimé] / Tanja JOVANOVIC, Auteur ; Ami SMITH, Auteur ; Asante KAMKWALALA, Auteur ; James POOLE, Auteur ; Tara SAMPLES, Auteur ; Seth D. NORRHOLM, Auteur ; Kerry J. RESSLER, Auteur ; Bekh BRADLEY, Auteur . - 2011 . - p.844-852. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 52-8 (August 2011) . - p.844-852 Mots-clés : Child abuse  maternal trauma  child anxiety  startle response  heart-rate variability Index. décimale : PER Périodiques Résumé : Background:  A growing number of studies indicate that low income, African American men and women living in urban environments are at high risk for trauma exposure, which may have intergenerational effects. The current study employed psychophysiological methods to describe biomarkers of anxiety in children of traumatized mothers. Methods:  Study participants were recruited from a highly traumatized urban population, comprising mother–child pairs (n = 36) that included school-age children. Mothers were assessed for childhood abuse with the Childhood Trauma Questionnaire, as well as symptoms of depression and posttraumatic stress disorder (PTSD). The children were measured for dark-enhanced startle responses and heart-rate variability. Results:  Dark-enhanced startle was found to be higher in children whose mothers had high levels of childhood physical abuse, as compared to children whose mothers had low levels of physical abuse. During the habituation phase of the startle experiment, children whose mothers had high levels of childhood emotional abuse had higher sympathetic system activation compared to children of mothers with low emotional abuse. These effects remained significant after accounting for maternal symptoms of PTSD and depression, as well as for the child’s trauma exposure. Conclusion:  These results demonstrate that children of mothers who have history of childhood physical and emotional abuse have higher dark-enhanced startle as well as greater sympathetic nervous system activation than children of mothers who do not report a history of childhood physical and emotional abuse, and emphasize the utility of physiological measures as pervasive biomarkers of psychopathology that can easily be measured in children. En ligne : http://dx.doi.org/10.1111/j.1469-7610.2011.02410.x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=132

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